Spenlé Caroline, Loustau Thomas, Murdamoothoo Devadarssen, Erne William, la Forest Divonne Stephanie Beghelli-de, Veber Romain, Petti Luciana, Bourdely Pierre, Mörgelin Matthias, Brauchle Eva-Maria, Cremel Gérard, Randrianarisoa Vony, Camara Abdouramane, Rekima Samah, Schaub Sebastian, Nouhen Kelly, Imhof Thomas, Hansen Uwe, Paul Nicodème, Carapito Raphael, Pythoud Nicolas, Hirschler Aurélie, Carapito Christine, Dumortier Hélène, Mueller Christopher G, Koch Manuel, Schenke-Layland Katja, Kon Shigeyuki, Sudaka Anne, Anjuère Fabienne, Obberghen-Schilling Ellen Van, Orend Gertraud
Tenascin-C Orchestrates an Immune-Suppressive Tumor Microenvironment in Oral Squamous Cell Carcinoma Article de journal
Dans: Cancer Immunology Research, vol. 8, no. 9, p. 1122–1138, 2020, ISSN: 2326-6074.
Résumé | Liens | BibTeX | Étiquettes: Dumortier, I2CT, Team-Dumortier, Team-Mueller
@article{spenle_tenascin-c_2020,
title = {Tenascin-C Orchestrates an Immune-Suppressive Tumor Microenvironment in Oral Squamous Cell Carcinoma},
author = {Caroline Spenlé and Thomas Loustau and Devadarssen Murdamoothoo and William Erne and Stephanie Beghelli-de la Forest Divonne and Romain Veber and Luciana Petti and Pierre Bourdely and Matthias Mörgelin and Eva-Maria Brauchle and Gérard Cremel and Vony Randrianarisoa and Abdouramane Camara and Samah Rekima and Sebastian Schaub and Kelly Nouhen and Thomas Imhof and Uwe Hansen and Nicodème Paul and Raphael Carapito and Nicolas Pythoud and Aurélie Hirschler and Christine Carapito and Hélène Dumortier and Christopher G Mueller and Manuel Koch and Katja Schenke-Layland and Shigeyuki Kon and Anne Sudaka and Fabienne Anjuère and Ellen Van Obberghen-Schilling and Gertraud Orend},
doi = {10.1158/2326-6066.CIR-20-0074},
issn = {2326-6074},
year = {2020},
date = {2020-09-01},
journal = {Cancer Immunology Research},
volume = {8},
number = {9},
pages = {1122--1138},
abstract = {Inherent immune suppression represents a major challenge in the treatment of human cancer. The extracellular matrix molecule tenascin-C promotes cancer by multiple mechanisms, yet the roles of tenascin-C in tumor immunity are incompletely understood. Using a 4NQO-induced oral squamous cell carcinoma (OSCC) model with abundant and absent tenascin-C, we demonstrated that tenascin-C enforced an immune-suppressive lymphoid stroma via CCL21/CCR7 signaling, leading to increased metastatic tumors. Through TLR4, tenascin-C increased expression of CCR7 in CD11c+ myeloid cells. By inducing CCL21 in lymphatic endothelial cells via integrin α9β1 and binding to CCL21, tenascin-C immobilized CD11c+ cells in the stroma. Inversion of the lymph node-to-tumor CCL21 gradient, recruitment of T regulatory cells, high expression of anti-inflammatory cytokines, and matrisomal components were hallmarks of the tenascin-C-instructed lymphoid stroma. Ablation of tenascin-C or CCR7 blockade inhibited the lymphoid immune-suppressive stromal properties, reducing tumor growth, progression, and metastasis. Thus, targeting CCR7 could be relevant in human head and neck tumors, as high tenascin-C expression and an immune-suppressive stroma correlate to poor patient survival.},
keywords = {Dumortier, I2CT, Team-Dumortier, Team-Mueller},
pubstate = {published},
tppubtype = {article}
}
Malanagahalli Sowmya, Murera Diane, Martín Cristina, Lin Hazel, Wadier Nadége, Dumortier Hélène, Vázquez Ester, Bianco Alberto
Few Layer Graphene Does Not Affect Cellular Homeostasis of Mouse Macrophages Article de journal
Dans: Nanomaterials (Basel, Switzerland), vol. 10, no. 2, 2020, ISSN: 2079-4991.
Résumé | Liens | BibTeX | Étiquettes: Autophagy, bone marrow derived macrophages, carbon nanomaterials, Dumortier, graphene, I2CT, primary immune cells, Team-Bianco, Team-Dumortier
@article{malanagahalli_few_2020,
title = {Few Layer Graphene Does Not Affect Cellular Homeostasis of Mouse Macrophages},
author = {Sowmya Malanagahalli and Diane Murera and Cristina Martín and Hazel Lin and Nadége Wadier and Hélène Dumortier and Ester Vázquez and Alberto Bianco},
doi = {10.3390/nano10020228},
issn = {2079-4991},
year = {2020},
date = {2020-01-01},
journal = {Nanomaterials (Basel, Switzerland)},
volume = {10},
number = {2},
abstract = {: Graphene-related materials (GRMs) are widely used in various applications due to their unique properties. A growing number of reports describe the impact of different carbon nanomaterials, including graphene oxide (GO), reduced GO (rGO), and carbon nanotubes (CNT), on immune cells, but there is still a very limited number of studies on graphene. In this work, we investigated the biological responses of few layer graphene (FLG) on mouse macrophages (bone marrow derived macrophages, BMDMs), which are part of the first line of defense in innate immunity. In particular, our paper describes our findings of short-term FLG treatment in BMDMs with a focus on observing material internalization and changes in general cell morphology. Subsequent investigation of cytotoxicity parameters showed that increasing doses of FLG did not hamper the viability of cells and did not trigger inflammatory responses. Basal level induced autophagic activity sufficed to maintain the cellular homeostasis of FLG treated cells. Our results shed light on the impact of FLG on primary macrophages and show that FLG does not elicit immunological responses leading to cell death.},
keywords = {Autophagy, bone marrow derived macrophages, carbon nanomaterials, Dumortier, graphene, I2CT, primary immune cells, Team-Bianco, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Murera Diane, Malaganahalli Sowmya, Martín Cristina, Reina Giacomo, Fauny Jean-Daniel, Dumortier Hélène, Vázquez Ester, Bianco Alberto
Few layer graphene does not affect the function and the autophagic activity of primary lymphocytes Article de journal
Dans: Nanoscale, vol. 11, no. 21, p. 10493–10503, 2019, ISSN: 2040-3372.
Résumé | Liens | BibTeX | Étiquettes: Animals, Autophagy, B-Lymphocytes, Dumortier, Graphite, I2CT, Inbred BALB C, Mice, Nanostructures, T-Lymphocytes, Team-Bianco, Team-Dumortier
@article{murera_few_2019,
title = {Few layer graphene does not affect the function and the autophagic activity of primary lymphocytes},
author = {Diane Murera and Sowmya Malaganahalli and Cristina Martín and Giacomo Reina and Jean-Daniel Fauny and Hélène Dumortier and Ester Vázquez and Alberto Bianco},
doi = {10.1039/c9nr00846b},
issn = {2040-3372},
year = {2019},
date = {2019-01-01},
journal = {Nanoscale},
volume = {11},
number = {21},
pages = {10493--10503},
abstract = {Carbon-based nanomaterials represent a new tool in future medical applications. Thus, focusing on the evaluation of the degree of their safety has been growing in the last years. In this study we were particularly interested in understanding the impact of few layer graphene (FLG) on primary murine lymphocytes. These B and T cells, that are the second, but specialized, line of defense of the immune system, rely on various mechanisms to ensure their efficient function and maintenance. One of these mechanisms is autophagy that can be triggered by various nanomaterials in some types of cells. For these reasons, we were interested in evaluating the way FLG could affect this process in lymphocytes. Our results point out that FLG neither impacts the viability and activation of T and B cells nor their autophagic activity. Using confocal microscopy, we were also able to see that FLG does not appear to cause any membrane damage and does not penetrate inside of these cells. Overall, our data do not show any effect of this material on lymphocyte homeostasis, which is one more argument in favor of the continuation of studies investigating the potential of FLG for therapeutic applications.},
keywords = {Animals, Autophagy, B-Lymphocytes, Dumortier, Graphite, I2CT, Inbred BALB C, Mice, Nanostructures, T-Lymphocytes, Team-Bianco, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Sawaf Matthieu, Fauny Jean-Daniel, Felten Renaud, Sagez Flora, Gottenberg Jacques-Eric, Dumortier Hélène, Monneaux Fanny
Defective BTLA functionality is rescued by restoring lipid metabolism in lupus CD4+ Ŧ cells Article de journal
Dans: JCI insight, vol. 3, no. 13, 2018, ISSN: 2379-3708.
Résumé | Liens | BibTeX | Étiquettes: 80 and over, Adolescent, Adult, Aged, Autoimmune Diseases, Autoimmunity, CD4-Positive T-Lymphocytes, Cell Proliferation, CTLA-4 Antigen, Dumortier, Female, France, Humans, I2CT, Imagerie, Immunologic, Immunology, Lipid Metabolism, lupus, Lupus Erythematosus, Lymphocyte Activation, Male, Middle Aged, Monneaux, Programmed Cell Death 1 Receptor, Receptors, Signal Transduction, Systemic, Team-Dumortier, Young Adult
@article{sawaf_defective_2018,
title = {Defective BTLA functionality is rescued by restoring lipid metabolism in lupus CD4+ Ŧ cells},
author = {Matthieu Sawaf and Jean-Daniel Fauny and Renaud Felten and Flora Sagez and Jacques-Eric Gottenberg and Hélène Dumortier and Fanny Monneaux},
doi = {10.1172/jci.insight.99711},
issn = {2379-3708},
year = {2018},
date = {2018-01-01},
journal = {JCI insight},
volume = {3},
number = {13},
abstract = {Coinhibitory receptors play an important role in the prevention of autoimmune diseases, such as systemic lupus erythematosus (SLE), by limiting T cell activation. B and T lymphocyte attenuator (BTLA) is an inhibitory receptor, similar to cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD1), that negatively regulates the immune response. The role of BTLA in the pathogenesis of autoimmune diseases in humans and, more specifically, in SLE is largely unknown. We investigated BTLA expression on various T cell subsets, and we did not observe significant variations of BTLA expression between lupus patients and healthy controls. However, the enhancement of BTLA expression after activation was significantly lower in SLE patients compared with that in healthy controls. Furthermore, we found an impaired capacity of BTLA to inhibit T cell activation in SLE due to a poor BTLA recruitment to the immunological synapse following T cell stimulation. Finally, we demonstrated that defective BTLA function can be corrected by restoring intracellular trafficking and by normalizing the lipid metabolism in lupus CD4+ T cells. Collectively, our results evidence that the BTLA signaling pathway is altered in SLE T cells and highlight the potential of targeting this pathway for the development of new therapeutic strategies in lupus.},
keywords = {80 and over, Adolescent, Adult, Aged, Autoimmune Diseases, Autoimmunity, CD4-Positive T-Lymphocytes, Cell Proliferation, CTLA-4 Antigen, Dumortier, Female, France, Humans, I2CT, Imagerie, Immunologic, Immunology, Lipid Metabolism, lupus, Lupus Erythematosus, Lymphocyte Activation, Male, Middle Aged, Monneaux, Programmed Cell Death 1 Receptor, Receptors, Signal Transduction, Systemic, Team-Dumortier, Young Adult},
pubstate = {published},
tppubtype = {article}
}
Gies Vincent, Wagner Alain, Seifert Cécile, Guffroy Aurélien, Fauny Jean-D., Knapp Anne-M., Pasquali Jean-L., Martin Thierry, Dumortier Hélène, Korganow Anne-S., Soulas-Sprauel Pauline
Identification of autoreactive B cells with labeled nucleosomes Article de journal
Dans: Scientific Reports, vol. 7, no. 1, p. 602, 2017, ISSN: 2045-2322.
Résumé | Liens | BibTeX | Étiquettes: Dumortier, I2CT, Imagerie, Team-Dumortier
@article{gies_identification_2017,
title = {Identification of autoreactive B cells with labeled nucleosomes},
author = {Vincent Gies and Alain Wagner and Cécile Seifert and Aurélien Guffroy and Jean-D. Fauny and Anne-M. Knapp and Jean-L. Pasquali and Thierry Martin and Hélène Dumortier and Anne-S. Korganow and Pauline Soulas-Sprauel},
doi = {10.1038/s41598-017-00664-0},
issn = {2045-2322},
year = {2017},
date = {2017-04-01},
journal = {Scientific Reports},
volume = {7},
number = {1},
pages = {602},
abstract = {The pathogenesis of autoimmune diseases has not been completely elucidated yet, and only a few specific treatments have been developed so far. In autoimmune diseases mediated by pathogenic autoantibodies, such as systemic lupus erythematosus, the specific detection and analysis of autoreactive B cells is crucial for a better understanding of the physiopathology. Biological characterization of these cells may help to define new therapeutic targets. Very few techniques allowing the precise detection of autoreactive B cells have been described so far. Herein we propose a new flow cytometry technique for specific detection of anti-nucleosome B cells, which secrete autoantibodies in systemic lupus erythematosus, using labeled nucleosomes. We produced different fluorochrome-labeled nucleosomes, characterized them, and finally tested them in flow cytometry. Nucleosomes labeled via the cysteines present in H3 histone specifically bind to autoreactive B cells in the anti-DNA transgenic B6.56R mice model. The present work validates the use of fluorochrome-labeled nucleosomes via cysteines to identify anti-nucleosome B cells and offers new opportunities for the description of autoreactive B cell phenotype.},
keywords = {Dumortier, I2CT, Imagerie, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Gies Vincent, Wagner Alain, Seifert Cécile, Guffroy Aurélien, Fauny Jean-D., Knapp Anne-M., Pasquali Jean-L., Martin Thierry, Dumortier Hélène, Korganow Anne-S., Soulas-Sprauel Pauline
Identification of autoreactive B cells with labeled nucleosomes Article de journal
Dans: Scientific Reports, vol. 7, no. 1, p. 602, 2017, ISSN: 2045-2322.
Résumé | Liens | BibTeX | Étiquettes: Animals, Autoantibodies, Autoantigens, Autoimmunity, B-Lymphocytes, Biomarkers, Cell Line, Dumortier, Female, Flow Cytometry, Humans, I2CT, Lupus Erythematosus, Mice, Nucleosomes, Staining and Labeling, Systemic, Team-Dumortier
@article{gies_identification_2017b,
title = {Identification of autoreactive B cells with labeled nucleosomes},
author = {Vincent Gies and Alain Wagner and Cécile Seifert and Aurélien Guffroy and Jean-D. Fauny and Anne-M. Knapp and Jean-L. Pasquali and Thierry Martin and Hélène Dumortier and Anne-S. Korganow and Pauline Soulas-Sprauel},
doi = {10.1038/s41598-017-00664-0},
issn = {2045-2322},
year = {2017},
date = {2017-01-01},
journal = {Scientific Reports},
volume = {7},
number = {1},
pages = {602},
abstract = {The pathogenesis of autoimmune diseases has not been completely elucidated yet, and only a few specific treatments have been developed so far. In autoimmune diseases mediated by pathogenic autoantibodies, such as systemic lupus erythematosus, the specific detection and analysis of autoreactive B cells is crucial for a better understanding of the physiopathology. Biological characterization of these cells may help to define new therapeutic targets. Very few techniques allowing the precise detection of autoreactive B cells have been described so far. Herein we propose a new flow cytometry technique for specific detection of anti-nucleosome B cells, which secrete autoantibodies in systemic lupus erythematosus, using labeled nucleosomes. We produced different fluorochrome-labeled nucleosomes, characterized them, and finally tested them in flow cytometry. Nucleosomes labeled via the cysteines present in H3 histone specifically bind to autoreactive B cells in the anti-DNA transgenic B6.56R mice model. The present work validates the use of fluorochrome-labeled nucleosomes via cysteines to identify anti-nucleosome B cells and offers new opportunities for the description of autoreactive B cell phenotype.},
keywords = {Animals, Autoantibodies, Autoantigens, Autoimmunity, B-Lymphocytes, Biomarkers, Cell Line, Dumortier, Female, Flow Cytometry, Humans, I2CT, Lupus Erythematosus, Mice, Nucleosomes, Staining and Labeling, Systemic, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Sawaf Matthieu, Dumortier Hélène, Monneaux Fanny
Follicular Helper Ŧ Cells in Systemic Lupus Erythematosus: Why Should They Be Considered as Interesting Therapeutic Targets? Article de journal
Dans: Journal of Immunology Research, vol. 2016, p. 5767106, 2016, ISSN: 2314-7156.
Résumé | Liens | BibTeX | Étiquettes: Adult, Autoantibodies, B-Lymphocytes, Cell Differentiation, Dumortier, Germinal Center, Helper-Inducer, Humans, I2CT, Lupus Erythematosus, Molecular Targeted Therapy, Monneaux, Plasma Cells, Systemic, T-Lymphocytes, Team-Dumortier
@article{sawaf_follicular_2016,
title = {Follicular Helper Ŧ Cells in Systemic Lupus Erythematosus: Why Should They Be Considered as Interesting Therapeutic Targets?},
author = {Matthieu Sawaf and Hélène Dumortier and Fanny Monneaux},
doi = {10.1155/2016/5767106},
issn = {2314-7156},
year = {2016},
date = {2016-01-01},
journal = {Journal of Immunology Research},
volume = {2016},
pages = {5767106},
abstract = {Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by B cell hyperactivity leading to the production of autoantibodies, some of which having a deleterious effect. Reducing autoantibody production thus represents a way of controlling lupus pathogenesis, and a better understanding of the molecular and cellular factors involved in the differentiation of B cells into plasma cells could allow identifying new therapeutic targets. Follicular helper T cells (TFH) represent a distinct subset of CD4(+) T cells specialized in providing help to B cells. They are required for the formation of germinal centers and the generation of long-lived serological memory and, as such, are suspected to play a central role in SLE. Recent advances in the field of TFH biology have allowed the identification of important molecular factors involved in TFH differentiation, regulation, and function. Interestingly, some of these TFH-related molecules have been described to be dysregulated in lupus patients. In the present review, we give an overview of the aberrant expression and/or function of such key players in lupus, and we highlight their potential as therapeutic targets.},
keywords = {Adult, Autoantibodies, B-Lymphocytes, Cell Differentiation, Dumortier, Germinal Center, Helper-Inducer, Humans, I2CT, Lupus Erythematosus, Molecular Targeted Therapy, Monneaux, Plasma Cells, Systemic, T-Lymphocytes, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Jacquemin Clément, Schmitt Nathalie, Contin-Bordes Cécile, Liu Yang, Narayanan Priya, Seneschal Julien, Maurouard Typhanie, Dougall David, Davizon Emily Spence, Dumortier Hélène, Douchet Isabelle, Raffray Loïc, Richez Christophe, Lazaro Estibaliz, Duffau Pierre, Truchetet Marie-Elise, Khoryati Liliane, Mercié Patrick, Couzi Lionel, Merville Pierre, Schaeverbeke Thierry, Viallard Jean-François, Pellegrin Jean-Luc, Moreau Jean-François, Muller Sylviane, Zurawski Sandy, Coffman Robert L, Pascual Virginia, Ueno Hideki, Blanco Patrick
OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting Ŧ Follicular Helper Response Article de journal
Dans: Immunity, vol. 42, no. 6, p. 1159–1170, 2015, ISSN: 1097-4180.
Résumé | Liens | BibTeX | Étiquettes: Adolescent, Adult, Aged, Antigen Presentation, B-Lymphocytes, Cell Differentiation, Cells, Cultured, Cytokines, Disease Progression, Dumortier, Female, Helper-Inducer, Humans, I2CT, Immunologic Memory, Inducible T-Cell Co-Stimulator Protein, Lupus Erythematosus, Lymphocyte Activation, Male, Middle Aged, Molecular Targeted Therapy, Myeloid Cells, OX40, OX40 Ligand, Receptors, RNA, Signal Transduction, Systemic, T-Lymphocytes, Team-Dumortier, Toll-Like Receptor 7, Young Adult
@article{jacquemin_ox40_2015,
title = {OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting Ŧ Follicular Helper Response},
author = {Clément Jacquemin and Nathalie Schmitt and Cécile Contin-Bordes and Yang Liu and Priya Narayanan and Julien Seneschal and Typhanie Maurouard and David Dougall and Emily Spence Davizon and Hélène Dumortier and Isabelle Douchet and Loïc Raffray and Christophe Richez and Estibaliz Lazaro and Pierre Duffau and Marie-Elise Truchetet and Liliane Khoryati and Patrick Mercié and Lionel Couzi and Pierre Merville and Thierry Schaeverbeke and Jean-François Viallard and Jean-Luc Pellegrin and Jean-François Moreau and Sylviane Muller and Sandy Zurawski and Robert L Coffman and Virginia Pascual and Hideki Ueno and Patrick Blanco},
doi = {10.1016/j.immuni.2015.05.012},
issn = {1097-4180},
year = {2015},
date = {2015-01-01},
journal = {Immunity},
volume = {42},
number = {6},
pages = {1159--1170},
abstract = {Increased activity of T follicular helper (Tfh) cells plays a major pathogenic role in systemic lupus erythematosus (SLE). However, the mechanisms that cause aberrant Tfh cell responses in SLE remain elusive. Here we showed the OX40 ligand (OX40L)-OX40 axis contributes to the aberrant Tfh response in SLE. OX40L was expressed by myeloid antigen-presenting cells (APCs), but not B cells, in blood and in inflamed tissues in adult and pediatric SLE patients. The frequency of circulating OX40L-expressing myeloid APCs positively correlated with disease activity and the frequency of ICOS(+) blood Tfh cells in SLE. OX40 signals promoted naive and memory CD4(+) T cells to express multiple Tfh cell molecules and were sufficient to induce them to become functional B cell helpers. Immune complexes containing RNA induced OX40L expression on myeloid APCs via TLR7 activation. Our study provides a rationale to target the OX40L-OX40 axis as a therapeutic modality for SLE.},
keywords = {Adolescent, Adult, Aged, Antigen Presentation, B-Lymphocytes, Cell Differentiation, Cells, Cultured, Cytokines, Disease Progression, Dumortier, Female, Helper-Inducer, Humans, I2CT, Immunologic Memory, Inducible T-Cell Co-Stimulator Protein, Lupus Erythematosus, Lymphocyte Activation, Male, Middle Aged, Molecular Targeted Therapy, Myeloid Cells, OX40, OX40 Ligand, Receptors, RNA, Signal Transduction, Systemic, T-Lymphocytes, Team-Dumortier, Toll-Like Receptor 7, Young Adult},
pubstate = {published},
tppubtype = {article}
}
Coz Carole Le, Joublin Aurélie, Pasquali Jean-Louis, Korganow Anne-Sophie, Dumortier Hélène, Monneaux Fanny
Circulating TFH subset distribution is strongly affected in lupus patients with an active disease Article de journal
Dans: PloS One, vol. 8, no. 9, p. e75319, 2013, ISSN: 1932-6203.
Résumé | Liens | BibTeX | Étiquettes: Adult, Aged, B-Lymphocytes, Case-Control Studies, CD4 Lymphocyte Count, CD5 Antigens, CXCR5, Cytokines, Dumortier, Female, Flow Cytometry, Helper-Inducer, Humans, I2CT, Immunoglobulin E, Immunologic Memory, Immunophenotyping, Interleukin-21, Lupus Erythematosus, Male, Middle Aged, Monneaux, Phenotype, Receptors, Systemic, T-Lymphocytes, Team-Dumortier, Th2 Cells, Young Adult
@article{le_coz_circulating_2013,
title = {Circulating TFH subset distribution is strongly affected in lupus patients with an active disease},
author = {Carole Le Coz and Aurélie Joublin and Jean-Louis Pasquali and Anne-Sophie Korganow and Hélène Dumortier and Fanny Monneaux},
doi = {10.1371/journal.pone.0075319},
issn = {1932-6203},
year = {2013},
date = {2013-01-01},
journal = {PloS One},
volume = {8},
number = {9},
pages = {e75319},
abstract = {Follicular helper T cells (TFH) represent a distinct subset of CD4(+) T cells specialized in providing help to B lymphocytes, which may play a central role in autoimmune diseases having a major B cell component such as systemic lupus erythematosus. Recently, TFH subsets that share common phenotypic and functional characteristics with TFH cells from germinal centers, have been described in the peripheral blood from healthy individuals. The aim of this study was to analyze the distribution of such populations in lupus patients. Circulating TFH cell subsets were defined by multicolor flow cytometry as TFH17 (CXCR3(-)CCR6(+)), TFH1 (CXCR3 (+) CCR6(-)) or TFH2 (CXCR3(-)CCR6(-)) cells among CXCR5 (+) CD45RA(-)CD4(+) T cells in the peripheral blood of 23 SLE patients and 23 sex and age-matched healthy controls. IL-21 receptor expression by B cells was analyzed by flow cytometry and the serum levels of IL-21 and Igs were determined by ELISA tests. We found that the TFH2 cell subset frequency is strongly and significantly increased in lupus patients with an active disease (SLEDAI scoretextgreater8), while the TFH1 cell subset percentage is greatly decreased. The TFH2 and TFH1 cell subset frequency alteration is associated with the presence of high Ig levels and autoantibodies in patient's sera. Moreover, the TFH2 cell subset enhancement correlates with an increased frequency of double negative memory B cells (CD27(-)IgD(-)CD19(+) cells) expressing the IL-21R. Finally, we found that IgE levels in lupus patients' sera correlate with disease activity and seem to be associated with high TFH2 cell subset frequency. In conclusion, our study describes for the first time the distribution of circulating TFH cell subsets in lupus patients. Interestingly, we found an increased frequency of TFH2 cells, which correlates with disease activity. Our results suggest that this subset might play a key role in lupus pathogenesis.},
keywords = {Adult, Aged, B-Lymphocytes, Case-Control Studies, CD4 Lymphocyte Count, CD5 Antigens, CXCR5, Cytokines, Dumortier, Female, Flow Cytometry, Helper-Inducer, Humans, I2CT, Immunoglobulin E, Immunologic Memory, Immunophenotyping, Interleukin-21, Lupus Erythematosus, Male, Middle Aged, Monneaux, Phenotype, Receptors, Systemic, T-Lymphocytes, Team-Dumortier, Th2 Cells, Young Adult},
pubstate = {published},
tppubtype = {article}
}
Dumortier Hélène
When carbon nanotubes encounter the immune system: desirable and undesirable effects Article de journal
Dans: Advanced Drug Delivery Reviews, vol. 65, no. 15, p. 2120–2126, 2013, ISSN: 1872-8294.
Résumé | Liens | BibTeX | Étiquettes: Animals, Biomedical application, carbon, Carbon nanotubes, Dumortier, Environmental Exposure, Functionalization, Humans, I2CT, Immune cell activation, Immune System, inflammation, Inhalation Exposure, Lymphocyte, Macrophage, Nanotubes, Occupational Exposure, Team-Dumortier, Toxicity
@article{dumortier_when_2013,
title = {When carbon nanotubes encounter the immune system: desirable and undesirable effects},
author = {Hélène Dumortier},
doi = {10.1016/j.addr.2013.09.005},
issn = {1872-8294},
year = {2013},
date = {2013-01-01},
journal = {Advanced Drug Delivery Reviews},
volume = {65},
number = {15},
pages = {2120--2126},
abstract = {The role of our immune system is to bring efficient protection against invasion by foreign elements, not only pathogens but also any material it may be in contact with. Nanoparticles may enter the body and encounter the immune system either intentionally (e.g. administration for biomedical application) or not (e.g. respiratory occupational exposure). Therefore, it is of fundamental importance to get a thorough knowledge of the way they interact with immune cells and all related consequences. Among nanomaterials, carbon nanotubes (CNTs) are of special interest because of their tremendous field of applications. Consequently, their increasing production, processing and eventual incorporation into new types of composites and/or into biological systems have raised fundamental issues regarding their potential impact on health. This review aims at giving an overview of the known desirable and undesirable effects of CNTs on the immune system, i.e. beneficial modulation of immune cells by CNTs engineered for biomedical applications versus toxicity, inflammation and unwanted immune reactions triggered by CNTs themselves.},
keywords = {Animals, Biomedical application, carbon, Carbon nanotubes, Dumortier, Environmental Exposure, Functionalization, Humans, I2CT, Immune cell activation, Immune System, inflammation, Inhalation Exposure, Lymphocyte, Macrophage, Nanotubes, Occupational Exposure, Team-Dumortier, Toxicity},
pubstate = {published},
tppubtype = {article}
}
Russier Julie, Treossi Emanuele, Scarsi Alessia, Perrozzi Francesco, Dumortier Hélène, Ottaviano Luca, Meneghetti Moreno, Palermo Vincenzo, Bianco Alberto
Evidencing the mask effect of graphene oxide: a comparative study on primary human and murine phagocytic cells Article de journal
Dans: Nanoscale, vol. 5, no. 22, p. 11234–11247, 2013, ISSN: 2040-3372.
Résumé | Liens | BibTeX | Étiquettes: Animals, Cell Survival, Cells, Cultured, Cytokines, Dumortier, Graphite, Humans, I2CT, Macrophages, Mice, Monocytes, Oxidative Stress, Oxides, Reactive Oxygen Species, Team-Bianco, Team-Dumortier
@article{russier_evidencing_2013,
title = {Evidencing the mask effect of graphene oxide: a comparative study on primary human and murine phagocytic cells},
author = {Julie Russier and Emanuele Treossi and Alessia Scarsi and Francesco Perrozzi and Hélène Dumortier and Luca Ottaviano and Moreno Meneghetti and Vincenzo Palermo and Alberto Bianco},
doi = {10.1039/c3nr03543c},
issn = {2040-3372},
year = {2013},
date = {2013-01-01},
journal = {Nanoscale},
volume = {5},
number = {22},
pages = {11234--11247},
abstract = {Graphene oxide (GO) is attracting an ever-growing interest in different fields and applications. Not much is known about the possible impact of GO sheet lateral dimensions on their effects in vitro, especially on human primary cells. In an attempt to address this issue, we present a study to evaluate, how highly soluble 2-dimensional GO constituted of large or small flakes affects human monocyte derived macrophages (hMDM). For this purpose, the lateral size of GO was tuned using sonication and three samples were obtained. The non sonicated one presented large flakes (textasciitilde1.32 μm) while sonication for 2 and 26 hours generated small (textasciitilde0.27 μm) and very small (textasciitilde0.13 μm) sheets of GO, respectively. Cell studies were then conducted to evaluate the cytotoxicity, the oxidative stress induction, the activation potential and the pro-inflammatory effects of these different types of GO at increasing concentrations. In comparison, the same experiments were run on murine intraperitoneal macrophages (mIPM). The interaction between GO and cells was further examined by TEM and Raman spectroscopy. Our data revealed that the GO sheet size had a significant impact on different cellular parameters (i.e. cellular viability, ROS generation, and cellular activation). Indeed, the more the lateral dimensions of GO were reduced, the higher were the cellular internalization and the effects on cellular functionality. Our data also revealed a particular interaction of GO flakes with the cellular membrane. In fact, a GO mask due to the parallel arrangement of the graphene sheets on the cellular surface was observed. Considering the mask effect, we have hypothesized that this particular contact between GO sheets and the cell membrane could either promote their internalization or isolate cells from their environment, thus possibly accounting for the following impact on cellular parameters.},
keywords = {Animals, Cell Survival, Cells, Cultured, Cytokines, Dumortier, Graphite, Humans, I2CT, Macrophages, Mice, Monocytes, Oxidative Stress, Oxides, Reactive Oxygen Species, Team-Bianco, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Lacotte Stéphanie, Decossas Marion, Coz Carole Le, Brun Susana, Muller Sylviane, Dumortier Hélène
Early differentiated CD138(high) MHCII+ IgG+ plasma cells express CXCR3 and localize into inflamed kidneys of lupus mice Article de journal
Dans: PloS One, vol. 8, no. 3, p. e58140, 2013, ISSN: 1932-6203.
Résumé | Liens | BibTeX | Étiquettes: Animals, Autoantibodies, Cell Differentiation, CXCR3, Dumortier, Gene Expression Regulation, Histocompatibility Antigens Class II, I2CT, Immunoglobulin G, Inbred BALB C, Kidney, Leukocyte Common Antigens, Lupus Nephritis, Mice, Plasma Cells, Receptors, Syndecan-1, Team-Dumortier
@article{lacotte_early_2013,
title = {Early differentiated CD138(high) MHCII+ IgG+ plasma cells express CXCR3 and localize into inflamed kidneys of lupus mice},
author = {Stéphanie Lacotte and Marion Decossas and Carole Le Coz and Susana Brun and Sylviane Muller and Hélène Dumortier},
doi = {10.1371/journal.pone.0058140},
issn = {1932-6203},
year = {2013},
date = {2013-01-01},
journal = {PloS One},
volume = {8},
number = {3},
pages = {e58140},
abstract = {Humoral responses are central to the development of chronic autoimmune diseases such as systemic lupus erythematosus. Indeed, autoantibody deposition is responsible for tissue damage, the kidneys being one of the main target organs. As the source of pathogenic antibodies, plasma cells are therefore critical players in this harmful scenario, both at systemic and local levels. The aim of the present study was to analyze plasma cells in NZB/W lupus mice and to get a better understanding of the mechanisms underlying their involvement in the renal inflammation process. Using various techniques (i.e. flow cytometry, quantitative PCR, ELISpot), we identified and extensively characterized three plasma cell intermediates, according to their B220/CD138/MHCII expression levels. Each of these cell subsets displays specific proliferation and antibody secretion capacities. Moreover, we evidenced that the inflammation-related CXCR3 chemokine receptor is uniquely expressed by CD138(high)MHCII(+) plasma cells, which encompass both short- and long-lived cells and mostly produce IgG (auto)antibodies. Expression of CXCR3 allows efficient chemotactic responsiveness of these cells to cognate chemokines, which production is up-regulated in the kidneys of diseased NZB/W mice. Finally, using fluorescence and electron microscopy, we demonstrated the presence of CD138(+)CXCR3(+)IgG(+) cells in inflammatory areas in the kidneys, where they are very likely involved in the injury process. Thus, early differentiated CD138(high)MHCII(+) rather than terminally differentiated CD138(high)MHCII(low) plasma cells may be involved in the renal inflammatory injury in lupus, due to CXCR3 expression and IgG secretion.},
keywords = {Animals, Autoantibodies, Cell Differentiation, CXCR3, Dumortier, Gene Expression Regulation, Histocompatibility Antigens Class II, I2CT, Immunoglobulin G, Inbred BALB C, Kidney, Leukocyte Common Antigens, Lupus Nephritis, Mice, Plasma Cells, Receptors, Syndecan-1, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Delogu Lucia Gemma, Venturelli Enrica, Manetti Roberto, Pinna Gérard Aimé, Carru Ciriaco, Madeddu Roberto, Murgia Luciano, Sgarrella Francesco, Dumortier Hélène, Bianco Alberto
Ex vivo impact of functionalized carbon nanotubes on human immune cells Article de journal
Dans: Nanomedicine (London, England), vol. 7, no. 2, p. 231–243, 2012, ISSN: 1748-6963.
Résumé | Liens | BibTeX | Étiquettes: carbon, Cells, Cultured, Cytokines, Dumortier, Humans, I2CT, Immunity, Innate, Materials Testing, Nanotubes, T-Lymphocytes, Team-Bianco, Team-Dumortier
@article{delogu_ex_2012,
title = {Ex vivo impact of functionalized carbon nanotubes on human immune cells},
author = {Lucia Gemma Delogu and Enrica Venturelli and Roberto Manetti and Gérard Aimé Pinna and Ciriaco Carru and Roberto Madeddu and Luciano Murgia and Francesco Sgarrella and Hélène Dumortier and Alberto Bianco},
doi = {10.2217/nnm.11.101},
issn = {1748-6963},
year = {2012},
date = {2012-02-01},
journal = {Nanomedicine (London, England)},
volume = {7},
number = {2},
pages = {231--243},
abstract = {AIM: Different studies, carried out by us and others, have investigated the impact of carbon nanotubes (CNTs) in vitro and in animal models. To date, only a few studies have been performed on human cells ex vivo. There is also a lack of comparison between CNTs with varied functionalization and structural properties and their impact on different cell types.
MATERIALS & METHODS: The present ex vivo human study focuses on the impact of a series of functionalized multiwalled CNTs on human T and B lymphocytes, natural killer (NK) cells and monocytes.
RESULTS: Smaller diameter nanotubes are internalized more efficiently. Viability assays displayed the absence of cytotoxicity of all multiwalled CNTs used. Activation assay demonstrated a strong effect on monocytes and NK cells.
CONCLUSION: Our results, on human cells ex vivo, confirmed previous studies demonstrating appropriately functionalized CNTs are nontoxic. The effects on cell functionality were significant for the monocytes and NK cells. These findings encourage the possible use of CNTs for biomedical applications either as carriers of therapeutic molecules or as immune modulator systems.},
keywords = {carbon, Cells, Cultured, Cytokines, Dumortier, Humans, I2CT, Immunity, Innate, Materials Testing, Nanotubes, T-Lymphocytes, Team-Bianco, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Lamanna Giuseppe, Russier Julie, Dumortier Hélène, Bianco Alberto
Enhancement of anti-inflammatory drug activity by multivalent adamantane-based dendrons Article de journal
Dans: Biomaterials, vol. 33, no. 22, p. 5610–5617, 2012, ISSN: 1878-5905.
Résumé | Liens | BibTeX | Étiquettes: Animals, Anti-Inflammatory Agents, Cell Line, Cell Survival, Dendrimers, Drug Synergism, Dumortier, I2CT, Ibuprofen, Macrophages, Mice, Team-Bianco, Team-Dumortier
@article{lamanna_enhancement_2012,
title = {Enhancement of anti-inflammatory drug activity by multivalent adamantane-based dendrons},
author = {Giuseppe Lamanna and Julie Russier and Hélène Dumortier and Alberto Bianco},
doi = {10.1016/j.biomaterials.2012.03.072},
issn = {1878-5905},
year = {2012},
date = {2012-01-01},
journal = {Biomaterials},
volume = {33},
number = {22},
pages = {5610--5617},
abstract = {We have developed a straightforward method to prepare 1(st) and 2(nd) generation adamantane-based dendrons, previously called HYDRAmers, bearing at the periphery the anti-inflammatory drug, ibuprofen. The multivalency effect on the drug activity was studied, demonstrating that our multivalent ibuprofen-dendron conjugates exert an enhanced anti-inflammatory activity compared to free ibuprofen, in vitro. These results provide insights into the effect of HYDRAmer multivalency on biological interactions for therapeutic applications.},
keywords = {Animals, Anti-Inflammatory Agents, Cell Line, Cell Survival, Dendrimers, Drug Synergism, Dumortier, I2CT, Ibuprofen, Macrophages, Mice, Team-Bianco, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Lacerda Lara, Russier Julie, Pastorin Giorgia, Herrero Antonia M, Venturelli Enrica, Dumortier Hélène, Al-Jamal Khuloud T, Prato Maurizio, Kostarelos Kostas, Bianco Alberto
Translocation mechanisms of chemically functionalised carbon nanotubes across plasma membranes Article de journal
Dans: Biomaterials, vol. 33, no. 11, p. 3334–3343, 2012, ISSN: 1878-5905.
Résumé | Liens | BibTeX | Étiquettes: Animals, carbon, Cell Line, Cell Membrane, Dumortier, I2CT, Macrophages, Mice, Nanotubes, Phagocytosis, Team-Bianco, Team-Dumortier
@article{lacerda_translocation_2012,
title = {Translocation mechanisms of chemically functionalised carbon nanotubes across plasma membranes},
author = {Lara Lacerda and Julie Russier and Giorgia Pastorin and Antonia M Herrero and Enrica Venturelli and Hélène Dumortier and Khuloud T Al-Jamal and Maurizio Prato and Kostas Kostarelos and Alberto Bianco},
doi = {10.1016/j.biomaterials.2012.01.024},
issn = {1878-5905},
year = {2012},
date = {2012-01-01},
journal = {Biomaterials},
volume = {33},
number = {11},
pages = {3334--3343},
abstract = {Understanding the mechanisms responsible for carbon nanotube (CNT) internalisation into live cells is considered critical both from a fundamental point of view and for further engineering of CNT-based delivery systems to intracellular targets. While several studies are focused on the development of such CNT-based delivery systems, attempts to systematically elucidate the cellular uptake mechanisms of CNTs are still rather limited. The aim of the present study is to evaluate the cellular internalisation of chemically functionalised multi-walled carbon nanotubes (f-MWCNTs) in the presence of different well-known cellular uptake inhibitors. Our data reveal how f-MWCNTs are able to translocate across cell membranes of both phagocytic and non-phagocytic cell lines. We have evidenced that at least 30-50% of f-MWCNTs are taken up by cells through an energy-independent mechanism. This characteristic makes nanotubes loaded with therapeutic or diagnostic cargos extremely interesting as the release of active molecules directly into the cytoplasm increase their biological activity and therapeutic efficacy.},
keywords = {Animals, carbon, Cell Line, Cell Membrane, Dumortier, I2CT, Macrophages, Mice, Nanotubes, Phagocytosis, Team-Bianco, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Gaillard Claire, Duval Monique, Dumortier Hélène, Bianco Alberto
Carbon nanotube-coupled cell adhesion peptides are non-immunogenic: a promising step toward new biomedical devices Article de journal
Dans: Journal of Peptide Science: An Official Publication of the European Peptide Society, vol. 17, no. 2, p. 139–142, 2011, ISSN: 1099-1387.
Résumé | Liens | BibTeX | Étiquettes: carbon, Dumortier, Enzyme-Linked Immunosorbent Assay, I2CT, Nanotubes, Peptides, Team-Bianco, Team-Dumortier
@article{gaillard_carbon_2011,
title = {Carbon nanotube-coupled cell adhesion peptides are non-immunogenic: a promising step toward new biomedical devices},
author = {Claire Gaillard and Monique Duval and Hélène Dumortier and Alberto Bianco},
doi = {10.1002/psc.1290},
issn = {1099-1387},
year = {2011},
date = {2011-02-01},
journal = {Journal of Peptide Science: An Official Publication of the European Peptide Society},
volume = {17},
number = {2},
pages = {139--142},
abstract = {Carbon nanotubes functionalized with cell adhesion peptides can be considered as novel, promising candidates for the development of advanced drug delivery systems or for designing new generation of self-assembling nerve 'bridges'. An important step toward the integration of these types of conjugates in living bodies is the assessment of their impact on the immune system. In this direction, an integrin-derived peptide has been covalently conjugated to carbon nanotubes. Following intraperitoneal administration, peptide-carbon nanotubes do not trigger an anti-peptide antibody production. Demonstration of the immune neutrality of peptide-carbon nanotubes reinforces their potential use as substrates for neuronal regeneration in vivo.},
keywords = {carbon, Dumortier, Enzyme-Linked Immunosorbent Assay, I2CT, Nanotubes, Peptides, Team-Bianco, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Lacotte Stéphanie, Dumortier Hélène, Décossas Marion, Briand Jean-Paul, Muller Sylviane
Identification of new pathogenic players in lupus: autoantibody-secreting cells are present in nephritic kidneys of (NZBxNZW)F1 mice Article de journal
Dans: Journal of Immunology (Baltimore, Md.: 1950), vol. 184, no. 7, p. 3937–3945, 2010, ISSN: 1550-6606.
Résumé | Liens | BibTeX | Étiquettes: Animals, Autoantibodies, Autoantigens, B-Lymphocytes, Dumortier, Enzyme-Linked Immunosorbent Assay, Female, Histones, I2CT, Immunoblotting, Immunohistochemistry, Inbred BALB C, Inbred NZB, Lupus Nephritis, Mice, Team-Dumortier
@article{lacotte_identification_2010,
title = {Identification of new pathogenic players in lupus: autoantibody-secreting cells are present in nephritic kidneys of (NZBxNZW)F1 mice},
author = {Stéphanie Lacotte and Hélène Dumortier and Marion Décossas and Jean-Paul Briand and Sylviane Muller},
doi = {10.4049/jimmunol.0902595},
issn = {1550-6606},
year = {2010},
date = {2010-04-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {184},
number = {7},
pages = {3937--3945},
abstract = {An important hallmark of systemic lupus erythematosus is the production of autoantibodies specific for nuclear Ags, among which nucleosomes and their constituents, DNA and histones. It is widely admitted that some of these autoantibodies contribute largely in lupus pathogenesis because of their nephritogenic potential. However, the underlying mechanisms are still debated. In this study, we analyzed the autoimmune response against histone H2B during the course of the disease in lupus-prone (NZBxNZW)F1 mice, both in lymphoid organs and kidneys, and we assessed its potential involvement in lupus pathogenicity. We found that the N-terminal region of histone H2B represents a preferential target for circulating autoantibodies, which kinetics of appearance positively correlates with disease development. Furthermore, immunization of preautoimmune (NZBxNZW)F1 mice with H2B peptide 1-25 accelerates the disease. Kidney eluates from diseased (NZBxNZW)F1 mice do contain IgG Abs reacting with this peptide, and this H2B sequence was found to be accessible to specific Ab probes in Ag-containing deposits detected in nephritic kidneys. Finally, compared with control normal mice and to young preautoimmune (NZBxNZW)F1 animals, the frequency of cells secreting autoantibodies reacting with peptide 1-25 was significantly raised in the spleen and bone marrow and most importantly on a pathophysiological point of view, locally, in nephritic kidneys of diseased (NZBxNZW)F1 mice. Altogether our results demonstrate the existence in (NZBxNZW)F1 mice of both a systemic and local B cell response targeting the N-terminal region of histone H2B, and highlight the potential implication of this nuclear domain in lupus pathology.},
keywords = {Animals, Autoantibodies, Autoantigens, B-Lymphocytes, Dumortier, Enzyme-Linked Immunosorbent Assay, Female, Histones, I2CT, Immunoblotting, Immunohistochemistry, Inbred BALB C, Inbred NZB, Lupus Nephritis, Mice, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Schett G, Dumortier H, Hoefler E, Muller S, Steiner G
B cell epitopes of the heterogeneous nuclear ribonucleoprotein A2: identification of a new specific antibody marker for active lupus disease Article de journal
Dans: Annals of the Rheumatic Diseases, vol. 68, no. 5, p. 729–735, 2009, ISSN: 1468-2060.
Résumé | Liens | BibTeX | Étiquettes: Autoantibodies, B-Lymphocyte, Biomarkers, Dumortier, Enzyme-Linked Immunosorbent Assay, Epitopes, Female, Follow-Up Studies, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Humans, I2CT, Lupus Erythematosus, Male, Rheumatic Diseases, Severity of Illness Index, Systemic, Team-Dumortier
@article{schett_b_2009,
title = {B cell epitopes of the heterogeneous nuclear ribonucleoprotein A2: identification of a new specific antibody marker for active lupus disease},
author = {G Schett and H Dumortier and E Hoefler and S Muller and G Steiner},
doi = {10.1136/ard.2007.087502},
issn = {1468-2060},
year = {2009},
date = {2009-05-01},
journal = {Annals of the Rheumatic Diseases},
volume = {68},
number = {5},
pages = {729--735},
abstract = {OBJECTIVES: Autoantibody formation and T cell reactivity against the heterogeneous nuclear ribonucleoprotein A2 (hnRNP-A2) has been observed in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Since no differences in epitope recognition were reported and the usefulness of anti-hnRNP-A2 antibodies as diagnostic markers of SLE is unknown, it was our objective to characterise linear B cell epitopes of hnRNP-A2 and to relate the anti-hnRNP-A2 antibody responses to disease activity and clinical features of SLE.
METHODS: Sequential serum samples from 15 patients with SLE and sera from patients with other rheumatic diseases and healthy subjects were investigated by ELISA for autoantibody reactivities against a set of 13 overlapping peptides spanning the RNA-binding region of hnRNP-A2. Antibody reactivity against the complete protein was determined by western immunoblotting and ELISA. SLE disease activity was assessed by European Consensus Lupus Activity Measure scores, by SLE Index scores and the British Isles Lupus Assessment index.
RESULTS: Anti-peptide antibody reactivities were found in 60% of SLE sera but in only 5% of control samples, and were mainly directed to four peptides, one of which (p155-175) appeared to be immunodominant. Antibodies to p155-175 were exclusively seen in patients with SLE and correlated with clinical disease activity as well as kidney and skin involvement. No correlations were found for the other anti-peptide antibody responses.
CONCLUSION: Peptide p155-175 encompasses a disease-specific immunodominant epitope of hnRNP-A2. Since antibodies to p155-175 correlate with disease activity and nephritis, they may be useful as markers for active SLE.},
keywords = {Autoantibodies, B-Lymphocyte, Biomarkers, Dumortier, Enzyme-Linked Immunosorbent Assay, Epitopes, Female, Follow-Up Studies, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Humans, I2CT, Lupus Erythematosus, Male, Rheumatic Diseases, Severity of Illness Index, Systemic, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Lacotte Stéphanie, Brun Susana, Muller Sylviane, Dumortier Hélène
CXCR3, inflammation, and autoimmune diseases Article de journal
Dans: Annals of the New York Academy of Sciences, vol. 1173, p. 310–317, 2009, ISSN: 1749-6632.
Résumé | Liens | BibTeX | Étiquettes: Animals, arthritis, Biological, Chemokine CXCL10, Chemokine CXCL11, Chemokine CXCL9, CXCR3, Dumortier, Humans, I2CT, inflammation, Lupus Erythematosus, Models, Receptors, rheumatoid, Systemic, Team-Dumortier
@article{lacotte_cxcr3_2009,
title = {CXCR3, inflammation, and autoimmune diseases},
author = {Stéphanie Lacotte and Susana Brun and Sylviane Muller and Hélène Dumortier},
doi = {10.1111/j.1749-6632.2009.04813.x},
issn = {1749-6632},
year = {2009},
date = {2009-01-01},
journal = {Annals of the New York Academy of Sciences},
volume = {1173},
pages = {310--317},
abstract = {CXCR3 is a G protein-coupled, seven-transmembrane receptor that binds and is activated by the three IFN-gamma-inducible chemokines of the CXC family named CXCL9, CXCL10, and CXCL11. These chemokines are not constitutively expressed but are up-regulated in a proinflammatory cytokine milieu. Consequently, their major function is to selectively recruit immune cells at inflammation sites, but they also play a role in angiogenesis mechanisms. In the last few years, strong experimental and clinical evidence has been obtained supporting the idea that the CXCR3 pathway is involved in the development of autoimmune diseases, especially by creating local amplification loops of inflammation in target organs, thereby inducing worsening of clinical manifestations. This article briefly reviews what we know today about the nature and functions of CXCR3, with special emphasis on its involvement in two main rheumatic systemic autoimmune diseases, namely rheumatoid arthritis and systemic lupus erythematosus.},
keywords = {Animals, arthritis, Biological, Chemokine CXCL10, Chemokine CXCL11, Chemokine CXCL9, CXCR3, Dumortier, Humans, I2CT, inflammation, Lupus Erythematosus, Models, Receptors, rheumatoid, Systemic, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Kwan Wing-Hong, Navarro-Sanchez Erika, Dumortier Hélène, Decossas Marion, Vachon Hortense, dos Santos Flavia Barreto, Fridman Hervé W, Rey Félix A, Harris Eva, Despres Philippe, Mueller Christopher G
Dermal-type macrophages expressing CD209/DC-SIGN show inherent resistance to dengue virus growth Article de journal
Dans: PLoS neglected tropical diseases, vol. 2, no. 10, p. e311, 2008, ISSN: 1935-2735.
Résumé | Liens | BibTeX | Étiquettes: C-Type, Cell Adhesion Molecules, Cell Line, Cell Surface, Cells, Cultured, Dengue, Dengue virus, Dumortier, Gene Expression, Humans, I2CT, Lectins, Macrophages, Protein Binding, Receptors, Skin, Team-Dumortier, Team-Mueller, Viral Envelope Proteins
@article{kwan_dermal-type_2008,
title = {Dermal-type macrophages expressing CD209/DC-SIGN show inherent resistance to dengue virus growth},
author = {Wing-Hong Kwan and Erika Navarro-Sanchez and Hélène Dumortier and Marion Decossas and Hortense Vachon and Flavia Barreto dos Santos and Hervé W Fridman and Félix A Rey and Eva Harris and Philippe Despres and Christopher G Mueller},
doi = {10.1371/journal.pntd.0000311},
issn = {1935-2735},
year = {2008},
date = {2008-01-01},
journal = {PLoS neglected tropical diseases},
volume = {2},
number = {10},
pages = {e311},
abstract = {BACKGROUND: An important question in dengue pathogenesis is the identity of immune cells involved in the control of dengue virus infection at the site of the mosquito bite. There is evidence that infection of immature myeloid dendritic cells plays a crucial role in dengue pathogenesis and that the interaction of the viral envelope E glycoprotein with CD209/DC-SIGN is a key element for their productive infection. Dermal macrophages express CD209, yet little is known about their role in dengue virus infection.
METHODS AND FINDINGS: Here, we showed that dermal macrophages bound recombinant envelope E glycoprotein fused to green fluorescent protein. Because dermal macrophages stain for IL-10 in situ, we generated dermal-type macrophages from monocytes in the presence of IL-10 to study their infection by dengue virus. The macrophages were able to internalize the virus, but progeny virus production was undetectable in the infected cells. In addition, no IFN-alpha was produced in response to the virus. The inability of dengue virus to grow in the macrophages was attributable to accumulation of internalized virus particles into poorly-acidified phagosomes.
CONCLUSIONS: Aborting infection by viral sequestration in early phagosomes would present a novel means to curb infection of enveloped virus and may constitute a prime defense system to prevent dengue virus spread shortly after the bite of the infected mosquito.},
keywords = {C-Type, Cell Adhesion Molecules, Cell Line, Cell Surface, Cells, Cultured, Dengue, Dengue virus, Dumortier, Gene Expression, Humans, I2CT, Lectins, Macrophages, Protein Binding, Receptors, Skin, Team-Dumortier, Team-Mueller, Viral Envelope Proteins},
pubstate = {published},
tppubtype = {article}
}
Habib Mohammed, Rivas Magali Noval, Chamekh Mustapha, Wieckowski Sébastien, Sun Weimin, Bianco Alberto, Trouche Nathalie, Chaloin Olivier, Dumortier Hélène, Goldman Michel, Guichard Gilles, Fournel Sylvie, Vray Bernard
Cutting edge: small molecule CD40 ligand mimetics promote control of parasitemia and enhance Ŧ cells producing IFN-gamma during experimental Trypanosoma cruzi infection Article de journal
Dans: Journal of Immunology (Baltimore, Md.: 1950), vol. 178, no. 11, p. 6700–6704, 2007, ISSN: 0022-1767.
Résumé | Liens | BibTeX | Étiquettes: Animals, CD40 Antigens, CD40 Ligand, Cell Line, Cells, Chagas Disease, Cultured, Dumortier, I2CT, Inbred BALB C, Inbred C57BL, Interferon-gamma, Knockout, Mice, Molecular Mimicry, Parasitemia, T-Lymphocyte Subsets, Team-Bianco, Team-Dumortier, Trypanosoma cruzi
@article{habib_cutting_2007,
title = {Cutting edge: small molecule CD40 ligand mimetics promote control of parasitemia and enhance Ŧ cells producing IFN-gamma during experimental Trypanosoma cruzi infection},
author = {Mohammed Habib and Magali Noval Rivas and Mustapha Chamekh and Sébastien Wieckowski and Weimin Sun and Alberto Bianco and Nathalie Trouche and Olivier Chaloin and Hélène Dumortier and Michel Goldman and Gilles Guichard and Sylvie Fournel and Bernard Vray},
doi = {10.4049/jimmunol.178.11.6700},
issn = {0022-1767},
year = {2007},
date = {2007-06-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {178},
number = {11},
pages = {6700--6704},
abstract = {Host resistance to Trypanosoma cruzi infection depends on a type 1 response characterized by a strong production of IL-12 and IFN-gamma. Amplifying this response through CD40 triggering results in control of parasitemia. Two newly synthesized molecules (textless3 kDa) mimicking trimeric CD40L (mini CD40Ls(-1) and (-2)) bind to CD40, activate murine dendritic cells, and elicit IL-12 production. Wild-type but not CD40 knockout mice exhibited a sharp decrease of parasitemia and mortality when inoculated with T. cruzi mixed with miniCD40Ls. Moreover, the immunosuppression induced by T. cruzi infection was impaired in mice treated with miniCD40Ls, as shown by proliferation of splenic lymphocytes, percentage of CD8(+) T cells, and IFN-gamma production. Mice surviving T. cruzi infection in the presence of miniCD40L(-1) were immunized against a challenge infection. Our results indicate that CD40L mimetics are effective in vivo and promote the control of T. cruzi infection by overcoming the immunosuppression usually induced by the parasites.},
keywords = {Animals, CD40 Antigens, CD40 Ligand, Cell Line, Cells, Chagas Disease, Cultured, Dumortier, I2CT, Inbred BALB C, Inbred C57BL, Interferon-gamma, Knockout, Mice, Molecular Mimicry, Parasitemia, T-Lymphocyte Subsets, Team-Bianco, Team-Dumortier, Trypanosoma cruzi},
pubstate = {published},
tppubtype = {article}
}
Dumortier Hélène, Lacotte Stéphanie, Pastorin Giorgia, Marega Riccardo, Wu Wei, Bonifazi Davide, Briand Jean-Paul, Prato Maurizio, Muller Sylviane, Bianco Alberto
Functionalized carbon nanotubes are non-cytotoxic and preserve the functionality of primary immune cells Article de journal
Dans: Nano Letters, vol. 6, no. 7, p. 1522–1528, 2006, ISSN: 1530-6984.
Résumé | Liens | BibTeX | Étiquettes: Amides, B-Lymphocytes, Biotechnology, carbon, Cell Survival, Cytokines, Dumortier, I2CT, Macrophages, Molecular Structure, Nanotubes, Oxidation-Reduction, T-Lymphocytes, Team-Bianco, Team-Dumortier
@article{dumortier_functionalized_2006,
title = {Functionalized carbon nanotubes are non-cytotoxic and preserve the functionality of primary immune cells},
author = {Hélène Dumortier and Stéphanie Lacotte and Giorgia Pastorin and Riccardo Marega and Wei Wu and Davide Bonifazi and Jean-Paul Briand and Maurizio Prato and Sylviane Muller and Alberto Bianco},
doi = {10.1021/nl061160x},
issn = {1530-6984},
year = {2006},
date = {2006-07-01},
journal = {Nano Letters},
volume = {6},
number = {7},
pages = {1522--1528},
abstract = {Carbon nanotubes are emerging as innovative tools in nanobiotechnology. However, their toxic effects on environment and health have become an issue of strong concern. In the present study, we address the impact of functionalized carbon nanotubes (f-CNTs) on cells of the immune system. We have prepared two types of f-CNTs, following the 1,3-dipolar cycloaddition reaction (f-CNTs 1 and 2) and the oxidation/amidation treatment (f-CNTs 3 and 4), respectively. We have found that both types of f-CNTs are uptaken by B and T lymphocytes as well as macrophages in vitro, without affecting cell viability. Subsequently, the functionality of the different cells was analyzed carefully. We discovered that f-CNT 1, which is highly water soluble, did not influence the functional activity of immunoregulatory cells. f-CNT 3, which instead possesses reduced solubility and forms mainly stable water suspensions, preserved lymphocytes' functionality while provoking secretion of proinflammatory cytokines by macrophages.},
keywords = {Amides, B-Lymphocytes, Biotechnology, carbon, Cell Survival, Cytokines, Dumortier, I2CT, Macrophages, Molecular Structure, Nanotubes, Oxidation-Reduction, T-Lymphocytes, Team-Bianco, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Fournel Sylvie, Wieckowski Sébastien, Sun Weimin, Trouche Nathalie, Dumortier Hélène, Bianco Alberto, Chaloin Olivier, Habib Mohammed, Peter Jean-Christophe, Schneider Pascal, Vray Bernard, Toes René E, Offringa Rienk, Melief Cornelis J M, Hoebeke Johan, Guichard Gilles
C3-symmetric peptide scaffolds are functional mimetics of trimeric CD40L Article de journal
Dans: Nature Chemical Biology, vol. 1, no. 7, p. 377–382, 2005, ISSN: 1552-4450.
Résumé | Liens | BibTeX | Étiquettes: Animals, Apoptosis, Biological, CD40 Antigens, CD40 Ligand, Cell Line, Dumortier, Humans, I2CT, Inbred BALB C, Mice, Models, Molecular Mimicry, Molecular Structure, Peptides, Protein Conformation, Protein Structure, Quaternary, Structure-Activity Relationship, Team-Bianco, Team-Dumortier, Time Factors, tumor
@article{fournel_c3-symmetric_2005,
title = {C3-symmetric peptide scaffolds are functional mimetics of trimeric CD40L},
author = {Sylvie Fournel and Sébastien Wieckowski and Weimin Sun and Nathalie Trouche and Hélène Dumortier and Alberto Bianco and Olivier Chaloin and Mohammed Habib and Jean-Christophe Peter and Pascal Schneider and Bernard Vray and René E Toes and Rienk Offringa and Cornelis J M Melief and Johan Hoebeke and Gilles Guichard},
doi = {10.1038/nchembio746},
issn = {1552-4450},
year = {2005},
date = {2005-12-01},
journal = {Nature Chemical Biology},
volume = {1},
number = {7},
pages = {377--382},
abstract = {Interaction between CD40, a member of the tumor necrosis factor receptor (TNFR) superfamily, and its ligand CD40L, a 39-kDa glycoprotein, is essential for the development of humoral and cellular immune responses. Selective blockade or activation of this pathway provides the ground for the development of new treatments against immunologically based diseases and malignancies. Like other members of the TNF superfamily, CD40L monomers self-assemble around a threefold symmetry axis to form noncovalent homotrimers that can each bind three receptor molecules. Here, we report on the structure-based design of small synthetic molecules with C3 symmetry that can mimic CD40L homotrimers. These molecules interact with CD40, compete with the binding of CD40L to CD40, and reproduce, to a certain extent, the functional properties of the much larger homotrimeric soluble CD40L. Architectures based on rigid C3-symmetric cores may thus represent a general approach to mimicking homotrimers of the TNF superfamily.},
keywords = {Animals, Apoptosis, Biological, CD40 Antigens, CD40 Ligand, Cell Line, Dumortier, Humans, I2CT, Inbred BALB C, Mice, Models, Molecular Mimicry, Molecular Structure, Peptides, Protein Conformation, Protein Structure, Quaternary, Structure-Activity Relationship, Team-Bianco, Team-Dumortier, Time Factors, tumor},
pubstate = {published},
tppubtype = {article}
}
Hayer Silvia, Tohidast-Akrad Makiyeh, Haralambous Silva, Jahn-Schmid Beatrice, Skriner Karl, Trembleau Sylvie, Dumortier Hélène, Pinol-Roma Serafin, Redlich Kurt, Schett Georg, Muller Sylviane, Kollias George, Smolen Josef, Steiner Günter
Dans: Journal of Immunology (Baltimore, Md.: 1950), vol. 175, no. 12, p. 8327–8336, 2005, ISSN: 0022-1767.
Résumé | Liens | BibTeX | Étiquettes: Animals, Antibody Formation, arthritis, Autoantibodies, Autoantigens, Dumortier, Gene Expression Regulation, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Humans, I2CT, Joints, Mice, rheumatoid, Team-Dumortier, Tissue Distribution, transgenic, Tumor Necrosis Factor-alpha
@article{hayer_aberrant_2005,
title = {Aberrant expression of the autoantigen heterogeneous nuclear ribonucleoprotein-A2 (RA33) and spontaneous formation of rheumatoid arthritis-associated anti-RA33 autoantibodies in TNF-alpha transgenic mice},
author = {Silvia Hayer and Makiyeh Tohidast-Akrad and Silva Haralambous and Beatrice Jahn-Schmid and Karl Skriner and Sylvie Trembleau and Hélène Dumortier and Serafin Pinol-Roma and Kurt Redlich and Georg Schett and Sylviane Muller and George Kollias and Josef Smolen and Günter Steiner},
doi = {10.4049/jimmunol.175.12.8327},
issn = {0022-1767},
year = {2005},
date = {2005-12-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {175},
number = {12},
pages = {8327--8336},
abstract = {Human TNF-alpha transgenic (hTNFtg) mice develop erosive arthritis closely resembling rheumatoid arthritis (RA). To investigate mechanisms leading to pathological autoimmune reactions in RA, we examined hTNFtg animals for the presence of RA-associated autoantibodies including Abs to citrullinated epitopes (anti-cyclic citrullinated peptide), heterogeneous nuclear ribonucleoprotein (hnRNP)-A2 (anti-RA33), and heat shock proteins (hsp) (anti-hsp). Although IgM anti-hsp Abs were detected in 40% of hTNFtg and control mice, IgG anti-hsp Abs were rarely seen, and anti-cyclic citrullinated peptide Abs were not seen at all. In contrast, textgreater50% of hTNFtg mice showed IgG anti-RA33 autoantibodies, which became detectable shortly after the onset of arthritis. These Abs were predominantly directed to a short epitope, which was identical with an epitope previously described in MRL/lpr mice. Incidence of anti-RA33 was significantly decreased in mice treated with the osteoclast inhibitor osteoprotegerin and also in c-fos-deficient mice lacking osteoclasts. Pronounced expression of hnRNP-A2 and a smaller splice variant was seen in joints of hTNFtg mice, whereas expression was low in control animals. Although the closely related hnRNP-A1 was also overexpressed, autoantibodies to this protein were infrequently detected. Because expression of hnRNP-A2 in thymus, spleen, brain, and lung was similar in hTNFtg and control mice, aberrant expression appeared to be restricted to the inflamed joint. Finally, immunization of hTNFtg mice with recombinant hnRNP-A2 or a peptide harboring the major B cell epitope aggravated arthritis. These findings suggest that overproduction of TNF-alpha leads to aberrant expression of hnRNP-A2 in the rheumatoid joint and subsequently to autoimmune reactions, which may enhance the inflammatory and destructive process.},
keywords = {Animals, Antibody Formation, arthritis, Autoantibodies, Autoantigens, Dumortier, Gene Expression Regulation, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Humans, I2CT, Joints, Mice, rheumatoid, Team-Dumortier, Tissue Distribution, transgenic, Tumor Necrosis Factor-alpha},
pubstate = {published},
tppubtype = {article}
}
Dumortier Hélène, van Mierlo Geertje J D, Egan Deirdre, van Ewijk Willem, Toes René E M, Offringa Rienk, Melief Cornelis J M
Dans: Journal of Immunology (Baltimore, Md.: 1950), vol. 175, no. 2, p. 855–863, 2005, ISSN: 0022-1767.
Résumé | Liens | BibTeX | Étiquettes: Adenovirus E1A Proteins, Animals, Antigen, Antigen Presentation, CD8-Positive T-Lymphocytes, Cell Differentiation, Cell Line, Cell Movement, Clonal Deletion, Cytotoxic, Cytotoxicity, Dendritic Cells, Down-Regulation, Dumortier, Epitopes, Female, I2CT, Immunologic, Immunologic Memory, Inbred C57BL, Lipopolysaccharides, Lymphocyte Activation, Mice, Myeloid Cells, Receptors, Regulatory, T-Cell, T-Lymphocyte, T-Lymphocytes, Team-Dumortier, transgenic
@article{dumortier_antigen_2005,
title = {Antigen presentation by an immature myeloid dendritic cell line does not cause CTL deletion in vivo, but generates CD8+ central memory-like Ŧ cells that can be rescued for full effector function},
author = {Hélène Dumortier and Geertje J D van Mierlo and Deirdre Egan and Willem van Ewijk and René E M Toes and Rienk Offringa and Cornelis J M Melief},
doi = {10.4049/jimmunol.175.2.855},
issn = {0022-1767},
year = {2005},
date = {2005-01-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {175},
number = {2},
pages = {855--863},
abstract = {Immature dendritic cells (DC), in contrast to their mature counterparts, are incapable of mobilizing a CD8+ CTL response, and, instead, have been reported to induce CTL tolerance. We directly addressed the impact of immature vs mature DC on CTL responses by infusing adenovirus peptide-loaded DC (of the D1 cell line) into mice that had received adenovirus-specific naive TCR-transgenic CD8+ T cells. Whereas i.v. injection of mature DC triggered vigorous CTL expansion, immature DC elicited little proliferation involving only a minority of the TCR-transgenic CTL. Even though the latter CTL developed effector functions, including cytolytic activity and proinflammatory cytokine secretion, these cells differed significantly from CTL primed by mature DC in that they did not exhibit down-regulation of CD62L and CCR7, receptors involved in trapping of T cells in the lymphoid organs. Interestingly, adoptive transfer of CTL effector cells harvested after priming by either mature or immature DC into naive recipient mice, followed by exposure to adenovirus, yielded quantitatively and qualitatively indistinguishable CTL memory responses. Therefore, in vivo priming of naive CD8+ T cells by immature DC, although failing to induce a full-blown, systemic CTL response, resulted in the formation of central memory-like T cells that were able to expand and produce IFN-gamma upon secondary antigenic stimulation.},
keywords = {Adenovirus E1A Proteins, Animals, Antigen, Antigen Presentation, CD8-Positive T-Lymphocytes, Cell Differentiation, Cell Line, Cell Movement, Clonal Deletion, Cytotoxic, Cytotoxicity, Dendritic Cells, Down-Regulation, Dumortier, Epitopes, Female, I2CT, Immunologic, Immunologic Memory, Inbred C57BL, Lipopolysaccharides, Lymphocyte Activation, Mice, Myeloid Cells, Receptors, Regulatory, T-Cell, T-Lymphocyte, T-Lymphocytes, Team-Dumortier, transgenic},
pubstate = {published},
tppubtype = {article}
}
van Mierlo Geertje J D, Boonman Zita F H M, Dumortier Hélène M H, den Boer Annemieke Th, Fransen Marieke F, Nouta Jan, van der Voort Ellen I H, Offringa Rienk, Toes René E M, Melief Cornelis J M
Activation of dendritic cells that cross-present tumor-derived antigen licenses CD8+ CTL to cause tumor eradication Article de journal
Dans: Journal of Immunology (Baltimore, Md.: 1950), vol. 173, no. 11, p. 6753–6759, 2004, ISSN: 0022-1767.
Résumé | Liens | BibTeX | Étiquettes: Adenovirus E1A Proteins, Animals, Antibodies, Antigen-Presenting Cells, Antigens, CD11c Antigen, CD40 Antigens, Cross-Priming, Cultured, Cytotoxic, Cytotoxicity, Dendritic Cells, Dumortier, Epitopes, Experimental, I2CT, Immunologic, Inbred C57BL, Injections, Intralesional, Intravenous, Knockout, Male, Mice, Monoclonal, Neoplasms, T-Lymphocyte, T-Lymphocytes, Team-Dumortier, transgenic, tumor, Tumor Cells, Viral
@article{van_mierlo_activation_2004,
title = {Activation of dendritic cells that cross-present tumor-derived antigen licenses CD8+ CTL to cause tumor eradication},
author = {Geertje J D van Mierlo and Zita F H M Boonman and Hélène M H Dumortier and Annemieke Th den Boer and Marieke F Fransen and Jan Nouta and Ellen I H van der Voort and Rienk Offringa and René E M Toes and Cornelis J M Melief},
doi = {10.4049/jimmunol.173.11.6753},
issn = {0022-1767},
year = {2004},
date = {2004-12-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {173},
number = {11},
pages = {6753--6759},
abstract = {The fate of naive CD8(+) T cells is determined by the environment in which they encounter MHC class I presented peptide Ags. The manner in which tumor Ags are presented is a longstanding matter of debate. Ag presentation might be mediated by tumor cells in tumor draining lymph nodes or via cross-presentation by professional APC. Either pathway is insufficient to elicit protective antitumor immunity. We now demonstrate using a syngeneic mouse tumor model, expressing an Ag derived from the early region 1A of human adenovirus type 5, that the inadequate nature of the antitumor CTL response is not due to direct Ag presentation by the tumor cells, but results from presentation of tumor-derived Ag by nonactivated CD11c(+) APC. Although this event results in division of naive CTL in tumor draining lymph nodes, it does not establish a productive immune response. Treatment of tumor-bearing mice with dendritic cell-stimulating agonistic anti-CD40 mAb resulted in systemic efflux of CTL with robust effector function capable to eradicate established tumors. For efficacy of anti-CD40 treatment, CD40 ligation of host APC is required because adoptive transfer of CD40-proficient tumor-specific TCR transgenic CTL into CD40-deficient tumor-bearing mice did not lead to productive antitumor immunity after CD40 triggering in vivo. CpG and detoxified LPS (MPL) acted similarly as agonistic anti-CD40 mAb with respect to CD8(+) CTL efflux and tumor eradication. Together these results indicate that dendritic cells, depending on their activation state, orchestrate the outcome of CTL-mediated immunity against tumors, leading either to an ineffective immune response or potent antitumor immunity.},
keywords = {Adenovirus E1A Proteins, Animals, Antibodies, Antigen-Presenting Cells, Antigens, CD11c Antigen, CD40 Antigens, Cross-Priming, Cultured, Cytotoxic, Cytotoxicity, Dendritic Cells, Dumortier, Epitopes, Experimental, I2CT, Immunologic, Inbred C57BL, Injections, Intralesional, Intravenous, Knockout, Male, Mice, Monoclonal, Neoplasms, T-Lymphocyte, T-Lymphocytes, Team-Dumortier, transgenic, tumor, Tumor Cells, Viral},
pubstate = {published},
tppubtype = {article}
}
Monneaux F, Dumortier H, Steiner G, Briand J P, Muller S
Murine models of systemic lupus erythematosus: B and Ŧ cell responses to spliceosomal ribonucleoproteins in MRL/Fas(lpr) and (NZB x NZW)F(1) lupus mice Article de journal
Dans: International Immunology, vol. 13, no. 9, p. 1155–1163, 2001, ISSN: 0953-8178.
Résumé | Liens | BibTeX | Étiquettes: Animals, Antibody Specificity, B-Lymphocytes, Crosses, Dumortier, fas Receptor, Female, Genetic, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Heterogeneous-Nuclear Ribonucleoproteins, Histocompatibility Antigens Class II, I2CT, Immunoglobulin G, Inbred MRL lpr, Inbred NZB, Lupus Erythematosus, Mice, Monneaux, Peptide Fragments, Ribonucleoprotein, Ribonucleoproteins, Small Nuclear, Species Specificity, Spliceosomes, Systemic, T-Lymphocytes, Team-Dumortier, U1 Small Nuclear
@article{monneaux_murine_2001,
title = {Murine models of systemic lupus erythematosus: B and Ŧ cell responses to spliceosomal ribonucleoproteins in MRL/Fas(lpr) and (NZB x NZW)F(1) lupus mice},
author = {F Monneaux and H Dumortier and G Steiner and J P Briand and S Muller},
doi = {10.1093/intimm/13.9.1155},
issn = {0953-8178},
year = {2001},
date = {2001-01-01},
journal = {International Immunology},
volume = {13},
number = {9},
pages = {1155--1163},
abstract = {(NZB x NZW)F(1) and MRL/Fas(lpr) lupus mice present a similar phenotype with a spectrum of autoantibodies associated with very severe nephritis. It is thought, however, that in contrast to other lupus-prone mice such as MRL/Fas(lpr) mice, (NZB x NZW)F(1) mice do not generate autoantibodies to ribonucleoproteins (RNP) Sm/RNP. In this study, we demonstrate that contrary to previous reports, the autoimmune response directed against Sm/RNP antigens also occurs in NZB x NZW mice. CD4(+) T cells from unprimed 10-week-old NZB x NZW mice proliferate and secrete IL-2 in response to peptide 131-151 of the U1-70K protein, which is known to contain a T(h) epitope recognized by CD4(+) T cells from MRL/Fas(lpr) mice. Peptide 131-151, which was found to bind I-A(k) and I-E(k) class II MHC molecules, also bound both I-A(d) and I-E(d) molecules. This result led us to also re-evaluate longitudinally the anti-Sm/RNP antibody response in NZB x NZW mice. We found that 25-week-old mice do produce antibodies reacting with several small nuclear and heterogeneous nuclear (hn) RNP proteins, such as SmD1, U1-70K and hnRNP A2/B1 proteins. The fine specificity of these antibodies was studied with overlapping synthetic peptides. The same antigenically positive and negative peptides were characterized in MRL/Fas(lpr) and NZB x NZW mice in the three proteins. This new finding can help to understand the mechanisms involved in the development of the anti-Sm/RNP antibody response and, particularly, the role played by non-MHC genes in this autoimmune response.},
keywords = {Animals, Antibody Specificity, B-Lymphocytes, Crosses, Dumortier, fas Receptor, Female, Genetic, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Heterogeneous-Nuclear Ribonucleoproteins, Histocompatibility Antigens Class II, I2CT, Immunoglobulin G, Inbred MRL lpr, Inbred NZB, Lupus Erythematosus, Mice, Monneaux, Peptide Fragments, Ribonucleoprotein, Ribonucleoproteins, Small Nuclear, Species Specificity, Spliceosomes, Systemic, T-Lymphocytes, Team-Dumortier, U1 Small Nuclear},
pubstate = {published},
tppubtype = {article}
}
Casimir J R, Iterbeke K, Nest W Van Den, Trescol-Biémont M C, Dumortier H, Muller S, Gerlier D, Rabourdin-Combe C, Tourwé D, Paris J
Conformational restriction of the Tyr53 side-chain in the decapeptide HE Article de journal
Dans: The Journal of Peptide Research: Official Journal of the American Peptide Society, vol. 56, no. 6, p. 398–408, 2000, ISSN: 1397-002X.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid Sequence, Animals, Antigen, Antigen-Presenting Cells, B-Lymphocytes, Chemical, Chickens, Dumortier, I2CT, Major Histocompatibility Complex, Mice, Models, Molecular Sequence Data, Muramidase, Peptide Biosynthesis, Peptides, Phenylalanine, Protein Binding, Protein Conformation, Receptors, T-Cell, Team-Dumortier, Temperature, Tyrosine
@article{casimir_conformational_2000,
title = {Conformational restriction of the Tyr53 side-chain in the decapeptide HE},
author = {J R Casimir and K Iterbeke and W Van Den Nest and M C Trescol-Biémont and H Dumortier and S Muller and D Gerlier and C Rabourdin-Combe and D Tourwé and J Paris},
doi = {10.1034/j.1399-3011.2000.00777.x},
issn = {1397-002X},
year = {2000},
date = {2000-12-01},
journal = {The Journal of Peptide Research: Official Journal of the American Peptide Society},
volume = {56},
number = {6},
pages = {398--408},
abstract = {A series of conformationally restricted analogs of the hen egg lysozyme (HEL) decapeptide 52-61 in which the conformationally flexible Tyr53 residue was replaced by several more constrained tyrosine and phenylalanine analogs was prepared. Among these tyrosine and phenylalanine analogs were 1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid (Htc), 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic), 4-amino- 1,2,4,5-tetrahydro-8-hydroxy-2-benzazepine-3-one (Hba), 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-one (Aba), 2-amino-6-hydroxytetralin-2-carboxylic acid (Hat) and 2-amino-5-hydroxyindan-2-carboxylic acid (Hai) in which the rotations around Calpha-Cbeta and Cbeta-Cgamma were restricted because of cyclization of the side-chain to the backbone. Synthesis of Pht-Hba-Gly-OH using a modification of the Flynn and de Laszlo procedure is described. Analogs of beta-methyltyrosine (beta-MeTyr) in which the side-chains were biased to particular side-chain torsional angles because of substitution at the beta-hydrogens were also prepared. These analogs of HEL[52-61] peptide were tested for their ability to bind to the major histocompatibility complex class II I-Ak molecule and to be recognized in this context by two T-cell hybridomas, specific for the parent peptide HEL[52-61]. The data showed that the conformation and also the configuration of the Tyr53 residue influenced both the binding of the peptide to I-Ak and the recognition of the peptide/I-Ak complex by a T-cell receptor.},
keywords = {Amino Acid Sequence, Animals, Antigen, Antigen-Presenting Cells, B-Lymphocytes, Chemical, Chickens, Dumortier, I2CT, Major Histocompatibility Complex, Mice, Models, Molecular Sequence Data, Muramidase, Peptide Biosynthesis, Peptides, Phenylalanine, Protein Binding, Protein Conformation, Receptors, T-Cell, Team-Dumortier, Temperature, Tyrosine},
pubstate = {published},
tppubtype = {article}
}
Dumortier H, Monneaux F, Jahn-Schmid B, Briand J P, Skriner K, Cohen P L, Smolen J S, Steiner G, Muller S
B and Ŧ cell responses to the spliceosomal heterogeneous nuclear ribonucleoproteins A2 and B1 in normal and lupus mice Article de journal
Dans: Journal of Immunology (Baltimore, Md.: 1950), vol. 165, no. 4, p. 2297–2305, 2000, ISSN: 0022-1767.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid Sequence, Animals, Autoantibodies, B-Lymphocytes, Dumortier, Epitope Mapping, Female, Heterogeneous Nuclear, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Heterogeneous-Nuclear Ribonucleoproteins, Humans, I2CT, Immunoglobulin G, Inbred BALB C, Inbred C57BL, Inbred CBA, Inbred MRL lpr, Injections, Lupus Nephritis, Lymphocyte Activation, Male, Mice, Molecular Sequence Data, Monneaux, Peptide Fragments, Recombinant Proteins, Ribonucleoproteins, RNA, Spliceosomes, Subcutaneous, T-Lymphocytes, Team-Dumortier, transgenic
@article{dumortier_b_2000,
title = {B and Ŧ cell responses to the spliceosomal heterogeneous nuclear ribonucleoproteins A2 and B1 in normal and lupus mice},
author = {H Dumortier and F Monneaux and B Jahn-Schmid and J P Briand and K Skriner and P L Cohen and J S Smolen and G Steiner and S Muller},
doi = {10.4049/jimmunol.165.4.2297},
issn = {0022-1767},
year = {2000},
date = {2000-08-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {165},
number = {4},
pages = {2297--2305},
abstract = {Autoantibodies directed against spliceosomal heterogeneous nuclear ribonucleoproteins (hnRNPs) are a typical feature of rheumatoid arthritis, systemic lupus erythematosus, and mixed-connective tissue disease. With the aim of investigating a potential pathogenic role of these Abs, we have studied the Ab response to A2/B1 hnRNPs in different murine models of lupus. The specificity of anti-A2/B1 Abs was tested with a series of 14 overlapping synthetic peptides covering the region 1-206 of A2 that contains most of the epitopes recognized by patients' Abs. A major epitope recognized very early during the course of the disease by Abs from most of MRL lpr/lpr mice but not from other lupus mice and from mice of different MHC haplotypes immunized against B1 was identified in residues 50-70. This peptide contains a highly conserved sequence RGFGFVTF also present in other hnRNPs and small nuclear ribonucleoproteins. Abs reacting with a second A2 epitope identified in residues 35-55 were detectable several weeks later, suggesting an intramolecular B cell epitope spreading during the course of the disease. We identified several T cell epitopes within the region 35-175 that generated an effective Th cell response with IL-2 and IFN-gamma secretion in nonautoimmune CBA/J mice sharing the same MHC haplotype H-2k as MRL/lpr mice. None of the peptides stimulated T cells primed in vivo with B1. Because Abs to peptide 50-70 were detected significantly earlier than Abs reacting with other A2 peptides and the protein itself, it is possible that within the protein, this segment contains residues playing an initiator role in the induction of the anti-A2/B1 and antispliceosome Ab response.},
keywords = {Amino Acid Sequence, Animals, Autoantibodies, B-Lymphocytes, Dumortier, Epitope Mapping, Female, Heterogeneous Nuclear, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Heterogeneous-Nuclear Ribonucleoproteins, Humans, I2CT, Immunoglobulin G, Inbred BALB C, Inbred C57BL, Inbred CBA, Inbred MRL lpr, Injections, Lupus Nephritis, Lymphocyte Activation, Male, Mice, Molecular Sequence Data, Monneaux, Peptide Fragments, Recombinant Proteins, Ribonucleoproteins, RNA, Spliceosomes, Subcutaneous, T-Lymphocytes, Team-Dumortier, transgenic},
pubstate = {published},
tppubtype = {article}
}
Dumortier H, Abbal M, Fort M, Briand J P, Cantagrel A, Muller S
MHC class II gene associations with autoantibodies to U1A and SmD1 proteins Article de journal
Dans: International Immunology, vol. 11, no. 2, p. 249–257, 1999, ISSN: 0953-8178.
Résumé | Liens | BibTeX | Étiquettes: Alleles, Antibody Specificity, Autoantibodies, Autoantigens, Autoimmune Diseases, Blotting, Dumortier, Enzyme-Linked Immunosorbent Assay, Genes, HLA-DP Antigens, HLA-DP beta-Chains, HLA-DQ Antigens, HLA-DQ beta-Chains, HLA-DR Antigens, HLA-DRB1 Chains, Humans, I2CT, MHC Class II, Peptides, Rheumatic Diseases, Ribonucleoprotein, Ribonucleoproteins, RNA-Binding Proteins, Small Nuclear, snRNP Core Proteins, Team-Dumortier, U1 Small Nuclear, Western
@article{dumortier_mhc_1999,
title = {MHC class II gene associations with autoantibodies to U1A and SmD1 proteins},
author = {H Dumortier and M Abbal and M Fort and J P Briand and A Cantagrel and S Muller},
doi = {10.1093/intimm/11.2.249},
issn = {0953-8178},
year = {1999},
date = {1999-01-01},
journal = {International Immunology},
volume = {11},
number = {2},
pages = {249--257},
abstract = {Autoantibodies against U small nuclear ribonucleoproteins (snRNP) are frequently present in the serum of patients with systemic rheumatic diseases, and have been reported to be associated with HLA-DR and -DQ genes. To better define the role of HLA genes in the production of such antibodies, we studied immunogenetic associations with autoantibodies reacting with U1 RNP, U1A and SmD1 proteins, and synthetic peptides containing immunodominant linear epitopes of these proteins. Only two out of the 15 overlapping peptides of U1A (i.e. peptides 35-58 and 257-282) and three of 11 peptides of SmD1 (i.e. peptides 1-20, 44-67 and 97-119) were significantly recognized by patients' sera selected on the basis of their antibody positivity with RNP in immunodiffusion. The distribution of DRB1, DQB1 and DPB1 alleles among the anti-RNP antibody-positive patients (n = 28) and healthy control subjects was similar. Antibodies against U1A (tested in Western immunoblotting with HeLa cell extracts) were positively associated to DRB1*06 allele; antibodies reacting with SmD1 peptide 44-67 were negatively associated to DRB1*02 and DQB1*0602 alleles. No association was found between DPB1 alleles and antibodies reacting with U1A and SmD1 antigens. This first study reporting an association between autoantibodies reacting with U1A and SmD1 proteins (and peptides of these proteins), and immunogenetic markers suggest that the production of antibody subsets directed against different components (or regions of these proteins) bound to the same snRNP particle is associated with distinct MHC class II alleles.},
keywords = {Alleles, Antibody Specificity, Autoantibodies, Autoantigens, Autoimmune Diseases, Blotting, Dumortier, Enzyme-Linked Immunosorbent Assay, Genes, HLA-DP Antigens, HLA-DP beta-Chains, HLA-DQ Antigens, HLA-DQ beta-Chains, HLA-DR Antigens, HLA-DRB1 Chains, Humans, I2CT, MHC Class II, Peptides, Rheumatic Diseases, Ribonucleoprotein, Ribonucleoproteins, RNA-Binding Proteins, Small Nuclear, snRNP Core Proteins, Team-Dumortier, U1 Small Nuclear, Western},
pubstate = {published},
tppubtype = {article}
}
Dumortier H, Gunnewiek J Klein, Roussel J P, van Aarssen Y, Briand J P, van Venrooij W J, Muller S
Dans: Nucleic Acids Research, vol. 26, no. 23, p. 5486–5491, 1998, ISSN: 0305-1048.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid Sequence, Animals, Dumortier, HeLa Cells, Humans, I2CT, Molecular Sequence Data, Peptide Fragments, Protein Binding, Rabbits, Ribonucleoprotein, Ribonucleoproteins, Small Nuclear, Solutions, Spliceosomes, Team-Dumortier, U1 Small Nuclear, Zinc, Zinc Fingers
@article{dumortier_at_1998,
title = {At least three linear regions but not the zinc-finger domain of U1C protein are exposed at the surface of the protein in solution and on the human spliceosomal U1 snRNP particle},
author = {H Dumortier and J Klein Gunnewiek and J P Roussel and Y van Aarssen and J P Briand and W J van Venrooij and S Muller},
doi = {10.1093/nar/26.23.5486},
issn = {0305-1048},
year = {1998},
date = {1998-12-01},
journal = {Nucleic Acids Research},
volume = {26},
number = {23},
pages = {5486--5491},
abstract = {No structural information on U1C protein either in its free state or bound to the spliceosomal U1 small nuclear ribonucleoprotein (snRNP) particle is currently available. Using rabbit antibodies raised against a complete set of 15 U1C overlapping synthetic peptides (16-30 residues long) in different immunochemical tests, linear regions exposed at the surface of free and U1 snRNP-bound U1C were identified. Epitopes within at least three regions spanning residues 31-62, 85-103 and 116-159 were recognized on free and plastic-immobilized recombinant human U1C expressed in Escherichia coli, on in vitro translated U1C protein and on U1C bound to the U1 snRNP particle present in HeLa S100 extract. Using a zinc affinity labeling method, we further showed that the N-terminal U1C peptide containing a zinc-finger motif (peptide 5-34) effectively binds65Zn2+. The N-terminal region of U1C, which is functional in U1 snRNP assembly, is apparently not located at the surface of the U1 snRNP particle.},
keywords = {Amino Acid Sequence, Animals, Dumortier, HeLa Cells, Humans, I2CT, Molecular Sequence Data, Peptide Fragments, Protein Binding, Rabbits, Ribonucleoprotein, Ribonucleoproteins, Small Nuclear, Solutions, Spliceosomes, Team-Dumortier, U1 Small Nuclear, Zinc, Zinc Fingers},
pubstate = {published},
tppubtype = {article}
}
Hoet R M, Raats J M, de Wildt R, Dumortier H, Muller S, van den Hoogen F, van Venrooij W J
Dans: Molecular Immunology, vol. 35, no. 16, p. 1045–1055, 1998, ISSN: 0161-5890.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid Sequence, Antibodies, Autoantibodies, Cross Reactions, Dumortier, Epitope Mapping, Genes, HeLa Cells, Humans, I2CT, Immunoglobulin, Immunoglobulin Fragments, Immunoglobulin Variable Region, Immunohistochemistry, Lupus Erythematosus, Monoclonal, Ribonucleoprotein, Ribonucleoproteins, Small Nuclear, Systemic, Team-Dumortier, U1 Small Nuclear
@article{hoet_human_1998,
title = {Human monoclonal autoantibody fragments from combinatorial antibody libraries directed to the U1snRNP associated U1C protein; epitope mapping, immunolocalization and V-gene usage},
author = {R M Hoet and J M Raats and R de Wildt and H Dumortier and S Muller and F van den Hoogen and W J van Venrooij},
doi = {10.1016/s0161-5890(98)00093-5},
issn = {0161-5890},
year = {1998},
date = {1998-11-01},
journal = {Molecular Immunology},
volume = {35},
number = {16},
pages = {1045--1055},
abstract = {To study the localization and function of the U1snRNP associated U1C protein, so far only human sera from systemic lupus erythematosus (SLE) overlap syndrome patients have been used. Here we report for the first time the isolation of human monoclonal anti-UIC autoantibody fragments from IgG derived combinatorial and semi-synthetic human antibody libraries. Two classes of human monoclonal anti-UIC (auto)antibodies were found: specific anti-U1C autoantibodies, recognizing U1C only, and cross-reactive antibodies which also react with U1A and Sm-B/B'proteins. The heavy chains (V(H)genes) of all five antibodies from the semi-synthetic libraries and two of the three U1C-specific patient derived autoantibody fragments are encoded by V(H)3 genes, in which V(H) 3-30 (DP-49) was overrepresented. The heavy chain of the two cross-reactive autoantibodies are derived from the 3-07 (DP-54) gene. Three epitope regions on the U1C protein are targeted by these antibodies. (1) Four U1C specific antibodies recognize an N-terminal region of U1C in which amino acids 30-63 are essential for recognition, (2) two antibodies recognize only the complete U1C protein, and (3) two cross-reactive and one U1C specific antibody recognize the C-terminal domain in which amino acids 98-126 are critical for recognition. The two cross-reactive antibodies (K 11 and K 15) recognize the proline-rich region of the U1C protein (amino acids 98 126) and cross-react with proline-rich regions in Sm-B/B' (amino acids 163-184) and U1A (amino acids 187-204). All 10 antibody fragments are able to immunoprecipitate the native U1snRNP particle. The two cross-reactive antibodies immunoprecipitate the other Sm containing snRNPs as well. Using confocal immunofluorescence microscopy we could show that the major part of the U1C protein is localized within the coiled body structure.},
keywords = {Amino Acid Sequence, Antibodies, Autoantibodies, Cross Reactions, Dumortier, Epitope Mapping, Genes, HeLa Cells, Humans, I2CT, Immunoglobulin, Immunoglobulin Fragments, Immunoglobulin Variable Region, Immunohistochemistry, Lupus Erythematosus, Monoclonal, Ribonucleoprotein, Ribonucleoproteins, Small Nuclear, Systemic, Team-Dumortier, U1 Small Nuclear},
pubstate = {published},
tppubtype = {article}
}
Mézière C, Viguier M, Dumortier H, Lo-Man R, Leclerc C, Guillet J G, Briand J P, Muller S
In vivo Ŧ helper cell response to retro-inverso peptidomimetics Article de journal
Dans: Journal of Immunology (Baltimore, Md.: 1950), vol. 159, no. 7, p. 3230–3237, 1997, ISSN: 0022-1767.
Résumé | BibTeX | Étiquettes: Amino Acid Sequence, Animals, Antibodies, Antigen, Capsid, Capsid Proteins, Dumortier, Female, Helper-Inducer, Histocompatibility Antigens Class II, I2CT, Immunoglobulin Allotypes, Immunoglobulin G, Inbred BALB C, Injections, Intraperitoneal, Lymphocyte Activation, Mice, Molecular Sequence Data, Peptide Fragments, Poliovirus, Protein Binding, Receptors, T-Cell, T-Lymphocytes, Team-Dumortier, Viral
@article{meziere_vivo_1997,
title = {In vivo Ŧ helper cell response to retro-inverso peptidomimetics},
author = {C Mézière and M Viguier and H Dumortier and R Lo-Man and C Leclerc and J G Guillet and J P Briand and S Muller},
issn = {0022-1767},
year = {1997},
date = {1997-10-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {159},
number = {7},
pages = {3230--3237},
abstract = {Peptide analogues containing reversed peptide bonds between each residue along the peptide sequence (retro-inverso modification) have been analyzed for their antigenic and in vivo immunogenic properties in the MHC II and Th cell response context. Two antigenic peptides were selected for this study, namely peptide 103-115 of poliovirus VP1, which is involved in the production of Abs that neutralize the infectivity of the virus, and peptide 435-446 from the third constant region of mouse heavy chain IgG2a allopeptide gamma 2ab, which mimics a corneal Ag implicated in autoimmune keratitis. In a competition assay performed in vitro using reference hybridomas of known MHC class II restriction, both retro-inverso analogues bound (although more weakly in our test) to I-Ad and/or I-Ed class II molecules. However, in both cases, this lower affinity was apparently largely compensated in vivo, as a T cell response (with IL-2 secretion), equivalent to that obtained with the wild-type peptides, was observed following immunization of BALB/c mice with the retro-inverso analogues. Moreover, these T cells proliferated and produced IL-2 in response to the cognate peptides. It is concluded that the T cell receptors of T cells primed in vivo with the retro-inverso analogues readily cross-react with parent and retro-inverso analogue-MHC complexes. The approach of using pseudopeptides containing changes involving the backbone, and not the orientation of side chains, may thus be promising to design potent immunogens for class II-restricted T cells.},
keywords = {Amino Acid Sequence, Animals, Antibodies, Antigen, Capsid, Capsid Proteins, Dumortier, Female, Helper-Inducer, Histocompatibility Antigens Class II, I2CT, Immunoglobulin Allotypes, Immunoglobulin G, Inbred BALB C, Injections, Intraperitoneal, Lymphocyte Activation, Mice, Molecular Sequence Data, Peptide Fragments, Poliovirus, Protein Binding, Receptors, T-Cell, T-Lymphocytes, Team-Dumortier, Viral},
pubstate = {published},
tppubtype = {article}
}
Halimi H, Dumortier H, Briand J P, Muller S
Comparison of two different methods using overlapping synthetic peptides for localizing linear B cell epitopes in the U1 snRNP-C autoantigen Article de journal
Dans: Journal of Immunological Methods, vol. 199, no. 1, p. 77–85, 1996, ISSN: 0022-1759.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid Sequence, Autoantigens, B-Lymphocytes, Dumortier, Enzyme-Linked Immunosorbent Assay, Epitope Mapping, Humans, I2CT, Lupus Erythematosus, Molecular Sequence Data, Peptides, Ribonucleoprotein, Systemic, Team-Dumortier, U1 Small Nuclear
@article{halimi_comparison_1996,
title = {Comparison of two different methods using overlapping synthetic peptides for localizing linear B cell epitopes in the U1 snRNP-C autoantigen},
author = {H Halimi and H Dumortier and J P Briand and S Muller},
doi = {10.1016/s0022-1759(96)00171-8},
issn = {0022-1759},
year = {1996},
date = {1996-11-01},
journal = {Journal of Immunological Methods},
volume = {199},
number = {1},
pages = {77--85},
abstract = {We have compared the performances of two different approaches using overlapping synthetic peptides to identify the location of linear epitopes of the U1 snRNP-C autoantigen. The first method was based on the use of 15 overlapping peptides (16-30 residue-long) synthesized using conventional Fmoc chemistry, removed from the resin by a standard cleavage procedure, and tested by ELISA after direct coating to polyvinyl microtiter plates. The second approach used a commercial kit (SPOT) to synthesize 75 overlapping decapeptides on cellulose membrane which were assayed by a direct immunoenzymatic test. Both standard and SPOTscan methods were evaluated with antibodies raised in rabbits against synthetic peptides of U1C and sera from patients with autoimmune diseases. In addition to inherent problems linked to the SPOT synthesis (in particular the impossibility of checking the quality of peptides), a number of limitations in the SPOTscan method were identified (e.g. a certain lack of sensitivity and, in one case, the complete lack of peptide reactivity due to the removal of charged end groups at both extremities). However, we found no background with sera from autoimmune patients in the SPOTscan and the antigenic maps obtained using the two approaches generally agreed. This study shows that the SPOTscan approach represents a simple, relatively non expensive and rapid method for initial screening to identify candidate sequences that may be dominant linear epitopes in a protein. Subsequent analysis and controls should include the preparation of conventionally synthesized peptides for formal immunochemical investigations.},
keywords = {Amino Acid Sequence, Autoantigens, B-Lymphocytes, Dumortier, Enzyme-Linked Immunosorbent Assay, Epitope Mapping, Humans, I2CT, Lupus Erythematosus, Molecular Sequence Data, Peptides, Ribonucleoprotein, Systemic, Team-Dumortier, U1 Small Nuclear},
pubstate = {published},
tppubtype = {article}
}
Briand J P, Guichard G, Dumortier H, Muller S
Retro-inverso peptidomimetics as new immunological probes. Validation and application to the detection of antibodies in rheumatic diseases Article de journal
Dans: The Journal of Biological Chemistry, vol. 270, no. 35, p. 20686–20691, 1995, ISSN: 0021-9258.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid Sequence, Animals, Antibodies, Autoantibodies, Autoimmune Diseases, Dumortier, Enzyme-Linked Immunosorbent Assay, Humans, I2CT, Immunoassay, Lupus Erythematosus, Mice, Molecular Sequence Data, Monoclonal, Peptide Fragments, Peptides, Rheumatic Diseases, Stereoisomerism, Structure-Activity Relationship, Systemic, Team-Dumortier
@article{briand_retro-inverso_1995,
title = {Retro-inverso peptidomimetics as new immunological probes. Validation and application to the detection of antibodies in rheumatic diseases},
author = {J P Briand and G Guichard and H Dumortier and S Muller},
doi = {10.1074/jbc.270.35.20686},
issn = {0021-9258},
year = {1995},
date = {1995-09-01},
journal = {The Journal of Biological Chemistry},
volume = {270},
number = {35},
pages = {20686--20691},
abstract = {Retro-inverso peptides which contain NH-CO bonds instead of CO-NH peptide bonds are much more resistant to proteolysis than L-peptides. Moreover, they have been shown recently to be able to mimic natural L-peptides with respect to poly- and monoclonal antibodies (Guichard, G., Benkirane, N., Zeder-Lutz, G., Van Regenmortel, M. H. V., Briand, J. P., and Muller, S. (1994b) Proc. Natl. Acad. Sci. U.S.A. 91, 9765-9769). We have further tested the capacity of retro-inverso peptidomimetics to serve as possible targets for antibodies produced by lupus mice and by patients with rheumatic autoimmune diseases. Several retro-inverso peptides corresponding to sequences known to be recognized by autoantibodies were synthesized, namely peptides 28-45 and 130-135 of H3, 277-291 of the Ro/SSA 52-kDa protein, and 304-324 of the Ro/SSA 60-kDa protein, and tested with autoimmune sera by enzyme-linked immunosorbent assay. We have found that retro-inverso peptides are recognized as well as or even better than natural peptides by antibodies from autoimmune patients and lupus mice. This new approach may lead to important progress in the future development of immunodiagnostic assays, particularly in the case of diseases characterized by inflammatory reactions in the course of which the level of degradative enzymes is increased.},
keywords = {Amino Acid Sequence, Animals, Antibodies, Autoantibodies, Autoimmune Diseases, Dumortier, Enzyme-Linked Immunosorbent Assay, Humans, I2CT, Immunoassay, Lupus Erythematosus, Mice, Molecular Sequence Data, Monoclonal, Peptide Fragments, Peptides, Rheumatic Diseases, Stereoisomerism, Structure-Activity Relationship, Systemic, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}