Publications
2015
Mairhofer David G, Ortner Daniela, Tripp Christoph H, Schaffenrath Sandra, Fleming Viktor, Heger Lukas, Komenda Kerstin, Reider Daniela, Dudziak Diana, Chen Suzie, Becker Jürgen C, Flacher Vincent, Stoitzner Patrizia
Impaired gp100-Specific CD8(+) Ŧ-Cell Responses in the Presence of Myeloid-Derived Suppressor Cells in a Spontaneous Mouse Melanoma Model Article de journal
Dans: The Journal of Investigative Dermatology, vol. 135, no. 11, p. 2785–2793, 2015, ISSN: 1523-1747.
Résumé | Liens | BibTeX | Étiquettes: Analysis of Variance, Animal, Animals, Antigen, cancer, CARCINOGENESIS, CD8-Positive T-Lymphocytes, Cell Proliferation, Cultured, DERMATOLOGY, development, disease, Disease Models, Experimental, GLYCOPROTEIN, gp100 Melanoma Antigen, Growth, Human, Humans, Immunity, Immunologic, IN VITRO, Inbred C57BL, iNOS, Leukocytes, LYMPH, LYMPH NODE, Lymph Nodes, Lymphocyte Activation, MELANOCYTES, Melanoma, Mice, mouse, murine, NITRIC OXIDE, nitric oxide synthase, Phenotype, Proliferation, Random Allocation, Receptor, Regulatory, RESPONSES, Skin, SUBSETS, Suppressor Factors, T CELLS, T-CELLS, T-Lymphocytes, Team-Mueller, Transforming Growth Factor beta, transgenic, tumor, Tumor Cells, tumor immunity
@article{mairhofer_impaired_2015,
title = {Impaired gp100-Specific CD8(+) Ŧ-Cell Responses in the Presence of Myeloid-Derived Suppressor Cells in a Spontaneous Mouse Melanoma Model},
author = {David G Mairhofer and Daniela Ortner and Christoph H Tripp and Sandra Schaffenrath and Viktor Fleming and Lukas Heger and Kerstin Komenda and Daniela Reider and Diana Dudziak and Suzie Chen and Jürgen C Becker and Vincent Flacher and Patrizia Stoitzner},
doi = {10.1038/jid.2015.241},
issn = {1523-1747},
year = {2015},
date = {2015-11-01},
journal = {The Journal of Investigative Dermatology},
volume = {135},
number = {11},
pages = {2785--2793},
abstract = {Murine tumor models that closely reflect human diseases are important tools to investigate carcinogenesis and tumor immunity. The transgenic (tg) mouse strain tg(Grm1)EPv develops spontaneous melanoma due to ectopic overexpression of the metabotropic glutamate receptor 1 (Grm1) in melanocytes. In the present study, we characterized the immune status and functional properties of immune cells in tumor-bearing mice. Melanoma development was accompanied by a reduction in the percentages of CD4(+) T cells including regulatory T cells (Tregs) in CD45(+) leukocytes present in tumor tissue and draining lymph nodes (LNs). In contrast, the percentages of CD8(+) T cells were unchanged, and these cells showed an activated phenotype in tumor mice. Endogenous melanoma-associated antigen glycoprotein 100 (gp100)-specific CD8(+) T cells were not deleted during tumor development, as revealed by pentamer staining in the skin and draining LNs. They, however, were unresponsive to ex vivo gp100-peptide stimulation in late-stage tumor mice. Interestingly, immunosuppressive myeloid-derived suppressor cells (MDSCs) were recruited to tumor tissue with a preferential accumulation of granulocytic MDSC (grMDSCs) over monocytic MDSC (moMDSCs). Both subsets produced Arginase-1, inducible nitric oxide synthase (iNOS), and transforming growth factor-β and suppressed T-cell proliferation in vitro. In this work, we describe the immune status of a spontaneous melanoma mouse model that provides an interesting tool to develop future immunotherapeutical strategies.},
keywords = {Analysis of Variance, Animal, Animals, Antigen, cancer, CARCINOGENESIS, CD8-Positive T-Lymphocytes, Cell Proliferation, Cultured, DERMATOLOGY, development, disease, Disease Models, Experimental, GLYCOPROTEIN, gp100 Melanoma Antigen, Growth, Human, Humans, Immunity, Immunologic, IN VITRO, Inbred C57BL, iNOS, Leukocytes, LYMPH, LYMPH NODE, Lymph Nodes, Lymphocyte Activation, MELANOCYTES, Melanoma, Mice, mouse, murine, NITRIC OXIDE, nitric oxide synthase, Phenotype, Proliferation, Random Allocation, Receptor, Regulatory, RESPONSES, Skin, SUBSETS, Suppressor Factors, T CELLS, T-CELLS, T-Lymphocytes, Team-Mueller, Transforming Growth Factor beta, transgenic, tumor, Tumor Cells, tumor immunity},
pubstate = {published},
tppubtype = {article}
}
2009
Chamouard Patrick, Monneaux Fanny, Richert Zoe, Voegeli Anne-Claire, Lavaux Thomas, Gaub Marie Pierre, Baumann René, Oudet Pierre, Muller Sylviane
Diminution of Circulating CD4+CD25 high Ŧ cells in naïve Crohn's disease Article de journal
Dans: Digestive Diseases and Sciences, vol. 54, no. 10, p. 2084–2093, 2009, ISSN: 1573-2568.
Résumé | Liens | BibTeX | Étiquettes: Adult, Aged, Blood Cell Count, CD4 Antigens, Colitis, Crohn Disease, Female, Flow Cytometry, Humans, I2CT, Interleukin-2 Receptor alpha Subunit, Lymphocyte Subsets, Male, Middle Aged, Monneaux, Regulatory, T-Lymphocytes, Team-Dumortier, Ulcerative
@article{chamouard_diminution_2009,
title = {Diminution of Circulating CD4+CD25 high Ŧ cells in naïve Crohn's disease},
author = {Patrick Chamouard and Fanny Monneaux and Zoe Richert and Anne-Claire Voegeli and Thomas Lavaux and Marie Pierre Gaub and René Baumann and Pierre Oudet and Sylviane Muller},
doi = {10.1007/s10620-008-0590-6},
issn = {1573-2568},
year = {2009},
date = {2009-10-01},
journal = {Digestive Diseases and Sciences},
volume = {54},
number = {10},
pages = {2084--2093},
abstract = {Crohn's disease is considered to be caused either by an excess of T-cell effector functions and/or by a defective regulatory T-cell compartment. The aim of this study was to assess in Crohn's disease the frequency of circulating CD4(+)CD25(high) T cells that possess regulatory T-cell functions and CD4(+)CD25(low) T cells that contain activated T cells. Flow cytometry of peripheral blood was used to assess CD4(+)CD25(high) and CD4(+)CD25(low) T-cell frequencies in a cohort of 66 patients with Crohn's disease in comparison to 19 patients with ulcerative colitis and 31 healthy individuals enrolled as controls. The CD4(+)CD25(high) T-cell frequency was significantly lowered in naïve Crohn's disease (P = 0.013) and in ulcerative colitis (P = 0.001). CD4(+)CD25(low) T-cell frequency was increased in Crohn's disease (P = 0.0001) and in ulcerative colitis (P = 0.0002). Both CD4(+)CD25(high) and CD4(+)CD25(low) T-cell frequencies are altered in naïve Crohn's disease resulting in an imbalance between both populations and a relative contraction of the CD4(+)CD25(high) T-cell population.},
keywords = {Adult, Aged, Blood Cell Count, CD4 Antigens, Colitis, Crohn Disease, Female, Flow Cytometry, Humans, I2CT, Interleukin-2 Receptor alpha Subunit, Lymphocyte Subsets, Male, Middle Aged, Monneaux, Regulatory, T-Lymphocytes, Team-Dumortier, Ulcerative},
pubstate = {published},
tppubtype = {article}
}
2008
Parietti Véronique, Monneaux Fanny, Décossas Marion, Muller Sylviane
Function of CD4+,CD25+ Treg cells in MRL/lpr mice is compromised by intrinsic defects in antigen-presenting cells and effector Ŧ cells Article de journal
Dans: Arthritis and Rheumatism, vol. 58, no. 6, p. 1751–1761, 2008, ISSN: 0004-3591.
Résumé | Liens | BibTeX | Étiquettes: Animal, Animals, Antigen-Presenting Cells, Antigens, B7-1 Antigen, B7-2 Antigen, CD, Cell Communication, Cells, Coculture Techniques, CTLA-4 Antigen, Cultured, Disease Models, Female, I2CT, Interleukin-1, Interleukin-2 Receptor alpha Subunit, Lupus Erythematosus, Mice, Monneaux, Regulatory, Systemic, T-Lymphocyte Subsets, T-Lymphocytes, Team-Dumortier
@article{parietti_function_2008,
title = {Function of CD4+,CD25+ Treg cells in MRL/lpr mice is compromised by intrinsic defects in antigen-presenting cells and effector Ŧ cells},
author = {Véronique Parietti and Fanny Monneaux and Marion Décossas and Sylviane Muller},
doi = {10.1002/art.23464},
issn = {0004-3591},
year = {2008},
date = {2008-06-01},
journal = {Arthritis and Rheumatism},
volume = {58},
number = {6},
pages = {1751--1761},
abstract = {OBJECTIVE: Naturally occurring CD4+,CD25+ Treg cells are central in the maintenance of peripheral tolerance. Impaired activity and/or a lower frequency of these cells is involved in the emergence of autoimmunity. We undertook this study to analyze relative proportions and functional alterations of Treg cells in MRL/lpr mice.
METHODS: The frequency of CD4+,CD25+ T cells in the peripheral blood of healthy and autoimmune mice was compared by flow cytometry. The capacity of CD4+,CD25+ T cells to inhibit the proliferation and cytokine secretion of CD4+,CD25- T cells was assessed after polyclonal activation.
RESULTS: MRL/lpr mice exhibited a normal percentage of CD4+,CD25 high T cells, and forkhead box P3 messenger RNA and protein expression in Treg cells was not altered. However, MRL/lpr Treg cells displayed a reduced capacity to suppress proliferation and to inhibit interferon-gamma secretion by syngeneic effector CD4+,CD25- T cells, as compared with syngeneic cocultures of CBA/J T cells. Moreover, effector MRL/lpr CD4+,CD25- T cells were substantially less susceptible to suppression even when cultured with CBA/J or MRL/lpr Treg cells. Crossover experiments led us to conclude that in MRL/lpr mice, each partner engaged in T cell regulation displays altered functions. Molecules involved in suppressive mechanisms (CTLA-4 and CD80/CD86) are underexpressed, and antigen-presenting cells (APCs) produce raised levels of interleukin-6, which is known to abrogate suppression.
CONCLUSION: Our results suggest that although the frequency and phenotype of Treg cells in MRL/lpr mice are similar to those in normal mice, Treg cells in MRL/lpr mice are not properly stimulated by APCs and are unable to suppress proinflammatory cytokine secretion from effector T cells.},
keywords = {Animal, Animals, Antigen-Presenting Cells, Antigens, B7-1 Antigen, B7-2 Antigen, CD, Cell Communication, Cells, Coculture Techniques, CTLA-4 Antigen, Cultured, Disease Models, Female, I2CT, Interleukin-1, Interleukin-2 Receptor alpha Subunit, Lupus Erythematosus, Mice, Monneaux, Regulatory, Systemic, T-Lymphocyte Subsets, T-Lymphocytes, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
METHODS: The frequency of CD4+,CD25+ T cells in the peripheral blood of healthy and autoimmune mice was compared by flow cytometry. The capacity of CD4+,CD25+ T cells to inhibit the proliferation and cytokine secretion of CD4+,CD25- T cells was assessed after polyclonal activation.
RESULTS: MRL/lpr mice exhibited a normal percentage of CD4+,CD25 high T cells, and forkhead box P3 messenger RNA and protein expression in Treg cells was not altered. However, MRL/lpr Treg cells displayed a reduced capacity to suppress proliferation and to inhibit interferon-gamma secretion by syngeneic effector CD4+,CD25- T cells, as compared with syngeneic cocultures of CBA/J T cells. Moreover, effector MRL/lpr CD4+,CD25- T cells were substantially less susceptible to suppression even when cultured with CBA/J or MRL/lpr Treg cells. Crossover experiments led us to conclude that in MRL/lpr mice, each partner engaged in T cell regulation displays altered functions. Molecules involved in suppressive mechanisms (CTLA-4 and CD80/CD86) are underexpressed, and antigen-presenting cells (APCs) produce raised levels of interleukin-6, which is known to abrogate suppression.
CONCLUSION: Our results suggest that although the frequency and phenotype of Treg cells in MRL/lpr mice are similar to those in normal mice, Treg cells in MRL/lpr mice are not properly stimulated by APCs and are unable to suppress proinflammatory cytokine secretion from effector T cells.
2007
Parietti Véronique, Chifflot Hélène, Muller Sylviane, Monneaux Fanny
Regulatory Ŧ cells and systemic lupus erythematosus Article de journal
Dans: Annals of the New York Academy of Sciences, vol. 1108, p. 64–75, 2007, ISSN: 0077-8923.
Résumé | Liens | BibTeX | Étiquettes: Animals, Autoimmunity, Humans, I2CT, Immune Tolerance, Lupus Erythematosus, Monneaux, Regulatory, Systemic, T-Lymphocyte Subsets, T-Lymphocytes, Team-Dumortier
@article{parietti_regulatory_2007,
title = {Regulatory Ŧ cells and systemic lupus erythematosus},
author = {Véronique Parietti and Hélène Chifflot and Sylviane Muller and Fanny Monneaux},
doi = {10.1196/annals.1422.007},
issn = {0077-8923},
year = {2007},
date = {2007-01-01},
journal = {Annals of the New York Academy of Sciences},
volume = {1108},
pages = {64--75},
abstract = {Regulatory T cells, especially CD4+CD25+ T cells, "natural killer" T cells and gammadelta T cells, are central in the maintenance of peripheral tolerance and the protection from the development of autoimmune diseases. Numerical or functional modifications of these cell populations were demonstrated to lead to the breakdown of tolerance and the emergence of autoimmunity. Involvement of regulatory T cells in the pathogenesis of systemic autoimmune diseases, such as systemic lupus erythematosus, might be of first importance. In murine models and patients with lupus, these regulatory T cells seem to be reduced in number. Functional deficiencies have also been described in a few studies. A better knowledge of regulatory T cell functional properties in systemic autoimmune diseases is essential to manipulate these cells and hopefully to restore immune tolerance.},
keywords = {Animals, Autoimmunity, Humans, I2CT, Immune Tolerance, Lupus Erythematosus, Monneaux, Regulatory, Systemic, T-Lymphocyte Subsets, T-Lymphocytes, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
2005
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}
}