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2010
Flacher Vincent, Tripp Christoph H, Stoitzner Patrizia, Haid Bernhard, Ebner Susanne, Frari Barbara Del, Koch Franz, Park Chae Gyu, Steinman Ralph M, Idoyaga Juliana, Romani Nikolaus
Epidermal Langerhans cells rapidly capture and present antigens from C-type lectin-targeting antibodies deposited in the dermis Journal Article
In: The Journal of Investigative Dermatology, vol. 130, no. 3, pp. 755–762, 2010, ISSN: 1523-1747.
Abstract | Links | BibTeX | Tags: Animals, Antibodies, antibody, Antigen, Antigen Presentation, ANTIGEN PRESENTING CELLS, Antigen-Presenting Cells, Antigens, BASEMENT MEMBRANE, C-Type, C-type lectin, CD103, CD8+ T cells, Cell Division, Cell Movement, Cells, Culture, Cultured, cytology, Dendritic Cells, DERMATOLOGY, DERMIS, Epidermal Cells, Epidermis, function, Human, Humans, Immunology, in situ, IN VITRO, In vivo, Inbred BALB C, Inbred C57BL, Injections, Intradermal, Langerhans Cells, LECTIN, Lectins, mAb, Mannose-Binding Lectins, Membrane, Mice, Monoclonal, mouse, murine, Pharmacology, Proliferation, Protein, Receptor, Skin, Surface, T CELLS, T-CELLS, T-Lymphocytes, Team-Mueller, Vaccination, vaccine, Vaccines
@article{flacher_epidermal_2010,
title = {Epidermal Langerhans cells rapidly capture and present antigens from C-type lectin-targeting antibodies deposited in the dermis},
author = {Vincent Flacher and Christoph H Tripp and Patrizia Stoitzner and Bernhard Haid and Susanne Ebner and Barbara Del Frari and Franz Koch and Chae Gyu Park and Ralph M Steinman and Juliana Idoyaga and Nikolaus Romani},
doi = {10.1038/jid.2009.343},
issn = {1523-1747},
year = {2010},
date = {2010-03-01},
journal = {The Journal of Investigative Dermatology},
volume = {130},
number = {3},
pages = {755--762},
abstract = {Antigen-presenting cells can capture antigens that are deposited in the skin, including vaccines given subcutaneously. These include different dendritic cells (DCs) such as epidermal Langerhans cells (LCs), dermal DCs, and dermal langerin+ DCs. To evaluate access of dermal antigens to skin DCs, we used mAb to two C-type lectin endocytic receptors, DEC-205/CD205 and langerin/CD207. When applied to murine and human skin explant cultures, these mAbs were efficiently taken up by epidermal LCs. In addition, anti-DEC-205 targeted langerin+ CD103+ and langerin- CD103- mouse dermal DCs. Unexpectedly, intradermal injection of either mAb, but not isotype control, resulted in strong and rapid labeling of LCs in situ, implying that large molecules can diffuse through the basement membrane into the epidermis. Epidermal LCs targeted in vivo by ovalbumin-coupled anti-DEC-205 potently presented antigen to CD4+ and CD8+ T cells in vitro. However, to our surprise, LCs targeted through langerin were unable to trigger T-cell proliferation. Thus, epidermal LCs have a major function in uptake of lectin-binding antibodies under standard vaccination conditions.},
keywords = {Animals, Antibodies, antibody, Antigen, Antigen Presentation, ANTIGEN PRESENTING CELLS, Antigen-Presenting Cells, Antigens, BASEMENT MEMBRANE, C-Type, C-type lectin, CD103, CD8+ T cells, Cell Division, Cell Movement, Cells, Culture, Cultured, cytology, Dendritic Cells, DERMATOLOGY, DERMIS, Epidermal Cells, Epidermis, function, Human, Humans, Immunology, in situ, IN VITRO, In vivo, Inbred BALB C, Inbred C57BL, Injections, Intradermal, Langerhans Cells, LECTIN, Lectins, mAb, Mannose-Binding Lectins, Membrane, Mice, Monoclonal, mouse, murine, Pharmacology, Proliferation, Protein, Receptor, Skin, Surface, T CELLS, T-CELLS, T-Lymphocytes, Team-Mueller, Vaccination, vaccine, Vaccines},
pubstate = {published},
tppubtype = {article}
}
Antigen-presenting cells can capture antigens that are deposited in the skin, including vaccines given subcutaneously. These include different dendritic cells (DCs) such as epidermal Langerhans cells (LCs), dermal DCs, and dermal langerin+ DCs. To evaluate access of dermal antigens to skin DCs, we used mAb to two C-type lectin endocytic receptors, DEC-205/CD205 and langerin/CD207. When applied to murine and human skin explant cultures, these mAbs were efficiently taken up by epidermal LCs. In addition, anti-DEC-205 targeted langerin+ CD103+ and langerin- CD103- mouse dermal DCs. Unexpectedly, intradermal injection of either mAb, but not isotype control, resulted in strong and rapid labeling of LCs in situ, implying that large molecules can diffuse through the basement membrane into the epidermis. Epidermal LCs targeted in vivo by ovalbumin-coupled anti-DEC-205 potently presented antigen to CD4+ and CD8+ T cells in vitro. However, to our surprise, LCs targeted through langerin were unable to trigger T-cell proliferation. Thus, epidermal LCs have a major function in uptake of lectin-binding antibodies under standard vaccination conditions.
2007
Mueller C G, Boix C, Kwan W H, Daussy C, Fournier E, Fridman W H, Molina T J
Critical role of monocytes to support normal B cell and diffuse large B cell lymphoma survival and proliferation Journal Article
In: Journal of Leukocyte Biology, vol. 82, no. 0741-5400 (Print), pp. 567–575, 2007.
Abstract | BibTeX | Tags: Activation, Antigen, Antigens, B CELL ACTIVATION, B CELLS, B-Cell, B-Cell Activation Factor Receptor, B-Lymphocytes, Biological, BLOOD, CC, CD14, CD40, Cell Division, Cell Proliferation, Cell Survival, Chemokine CCL5, chemokines, Coculture, cytology, Dendritic Cells, Differentiation, Diffuse, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Human, Humans, IL-2, Immunoenzyme Techniques, Interleukin-2, Large B-Cell, Lymph Nodes, LYMPHOMA, metabolism, monocyte, Monocytes, Myeloid Cells, pathology, Proliferation, Protein, Receptor, Reverse Transcriptase Polymerase Chain Reaction, survival, Team-Mueller, tumor, Tumor Markers
@article{mueller_critical_2007,
title = {Critical role of monocytes to support normal B cell and diffuse large B cell lymphoma survival and proliferation},
author = {C G Mueller and C Boix and W H Kwan and C Daussy and E Fournier and W H Fridman and T J Molina},
year = {2007},
date = {2007-01-01},
journal = {Journal of Leukocyte Biology},
volume = {82},
number = {0741-5400 (Print)},
pages = {567--575},
abstract = {Large B cell lymphomas can comprise numerous CD14+ cells in the tumor stroma, which raises the question of whether monocytes can support B cell survival and proliferation. We show that the coculture of monocytes with B cells from peripheral blood or from diffuse large B cell lymphoma enabled prolonged B cell survival. Under these conditions, diffuse large lymphoma B cells proliferated, and addition of B cell-activating factor of the TNF family (BAFF) and IL-2 enhanced cell division. Monocytes and dendritic cells (DC) had similar antiapoptotic activity on healthy B cells but displayed differences with respect to B cell proliferation. Monocytes and cord blood-derived CD14+ cells promoted B cell proliferation in the presence of an anti-CD40 stimulus, whereas DC supported B cell proliferation when activated through the BCR. DC and CD14+ cells were able to induce plasmocyte differentiation. When B cells were activated via the BCR or CD40, they released the leukocyte attractant CCL5, and this chemokine is one of the main chemokines expressed in diffuse large B cell lymphoma. The data support the notion that large B cell lymphoma recruit monocytes via CCL5 to support B cell survival and proliferation},
keywords = {Activation, Antigen, Antigens, B CELL ACTIVATION, B CELLS, B-Cell, B-Cell Activation Factor Receptor, B-Lymphocytes, Biological, BLOOD, CC, CD14, CD40, Cell Division, Cell Proliferation, Cell Survival, Chemokine CCL5, chemokines, Coculture, cytology, Dendritic Cells, Differentiation, Diffuse, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Human, Humans, IL-2, Immunoenzyme Techniques, Interleukin-2, Large B-Cell, Lymph Nodes, LYMPHOMA, metabolism, monocyte, Monocytes, Myeloid Cells, pathology, Proliferation, Protein, Receptor, Reverse Transcriptase Polymerase Chain Reaction, survival, Team-Mueller, tumor, Tumor Markers},
pubstate = {published},
tppubtype = {article}
}
Large B cell lymphomas can comprise numerous CD14+ cells in the tumor stroma, which raises the question of whether monocytes can support B cell survival and proliferation. We show that the coculture of monocytes with B cells from peripheral blood or from diffuse large B cell lymphoma enabled prolonged B cell survival. Under these conditions, diffuse large lymphoma B cells proliferated, and addition of B cell-activating factor of the TNF family (BAFF) and IL-2 enhanced cell division. Monocytes and dendritic cells (DC) had similar antiapoptotic activity on healthy B cells but displayed differences with respect to B cell proliferation. Monocytes and cord blood-derived CD14+ cells promoted B cell proliferation in the presence of an anti-CD40 stimulus, whereas DC supported B cell proliferation when activated through the BCR. DC and CD14+ cells were able to induce plasmocyte differentiation. When B cells were activated via the BCR or CD40, they released the leukocyte attractant CCL5, and this chemokine is one of the main chemokines expressed in diffuse large B cell lymphoma. The data support the notion that large B cell lymphoma recruit monocytes via CCL5 to support B cell survival and proliferation
2004
Monneaux Fanny, Parietti Véronique, Briand Jean-Paul, Muller Sylviane
Intramolecular Ŧ cell spreading in unprimed MRL/lpr mice: importance of the U1-70k protein sequence 131-151 Journal Article
In: Arthritis and Rheumatism, vol. 50, no. 10, pp. 3232–3238, 2004, ISSN: 0004-3591.
Abstract | Links | BibTeX | Tags: Animals, Cell Division, Female, I2CT, Immunization, Inbred BALB C, Inbred MRL lpr, Lupus Erythematosus, Lymphocytes, Mice, Monneaux, Peptides, Phosphorylation, Ribonucleoprotein, Systemic, Team-Dumortier, U1 Small Nuclear
@article{monneaux_intramolecular_2004,
title = {Intramolecular Ŧ cell spreading in unprimed MRL/lpr mice: importance of the U1-70k protein sequence 131-151},
author = {Fanny Monneaux and Véronique Parietti and Jean-Paul Briand and Sylviane Muller},
doi = {10.1002/art.20510},
issn = {0004-3591},
year = {2004},
date = {2004-10-01},
journal = {Arthritis and Rheumatism},
volume = {50},
number = {10},
pages = {3232--3238},
abstract = {OBJECTIVE: To analyze spontaneous T cell spreading against determinants of the U1-70K protein in young autoimmune MRL/lpr lupus mice, in comparison with the T cell spreading occurring in normal BALB/c mice immunized with peptide 131-151 of this protein.
METHODS: Peripheral blood lymphocytes (PBLs) from both unprimed MRL/lpr mice and immunized BALB/c mice were tested for their ability to proliferate ex vivo in response to 18 overlapping peptides of the U1-70K spliceosomal protein, using assays for lymphocyte proliferation and secretion of interleukin-2.
RESULTS: The proliferative response to peptides of the U1-70K protein evolved rapidly in MRL/lpr mice tested at different ages. At least 5 peptides were recognized by PBLs from 8-week-old autoimmune mice, whereas a different peptide was recognized by PBLs from MRL/lpr mice at 12 weeks of age. At 15 weeks, the proliferative response was weak or negative when assessed with any of the test peptides. At least 2 major peptides recognized by MRL/lpr PBLs were also recognized by PBLs generated in the BALB/c mice primed with peptide 131-151. We further demonstrated that, in preautoimmune MRL/lpr mice, repeated administration of phosphorylated peptide 131-151 (called P140), which was shown previously to be protective, transiently abolished T cell intramolecular spreading to other regions of the 70K protein.
CONCLUSION: This is the first study to demonstrate that intramolecular T cell spreading effectively occurs in MRL/lpr mice with lupus, and that region 131-151 is important in the cascade of events observed in the murine lupus response. This sequence might originate a mechanism of tolerance spreading that leads to the beneficial effect observed in MRL/lpr mice after treatment with the phosphorylated peptide 131-151.},
keywords = {Animals, Cell Division, Female, I2CT, Immunization, Inbred BALB C, Inbred MRL lpr, Lupus Erythematosus, Lymphocytes, Mice, Monneaux, Peptides, Phosphorylation, Ribonucleoprotein, Systemic, Team-Dumortier, U1 Small Nuclear},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: To analyze spontaneous T cell spreading against determinants of the U1-70K protein in young autoimmune MRL/lpr lupus mice, in comparison with the T cell spreading occurring in normal BALB/c mice immunized with peptide 131-151 of this protein.
METHODS: Peripheral blood lymphocytes (PBLs) from both unprimed MRL/lpr mice and immunized BALB/c mice were tested for their ability to proliferate ex vivo in response to 18 overlapping peptides of the U1-70K spliceosomal protein, using assays for lymphocyte proliferation and secretion of interleukin-2.
RESULTS: The proliferative response to peptides of the U1-70K protein evolved rapidly in MRL/lpr mice tested at different ages. At least 5 peptides were recognized by PBLs from 8-week-old autoimmune mice, whereas a different peptide was recognized by PBLs from MRL/lpr mice at 12 weeks of age. At 15 weeks, the proliferative response was weak or negative when assessed with any of the test peptides. At least 2 major peptides recognized by MRL/lpr PBLs were also recognized by PBLs generated in the BALB/c mice primed with peptide 131-151. We further demonstrated that, in preautoimmune MRL/lpr mice, repeated administration of phosphorylated peptide 131-151 (called P140), which was shown previously to be protective, transiently abolished T cell intramolecular spreading to other regions of the 70K protein.
CONCLUSION: This is the first study to demonstrate that intramolecular T cell spreading effectively occurs in MRL/lpr mice with lupus, and that region 131-151 is important in the cascade of events observed in the murine lupus response. This sequence might originate a mechanism of tolerance spreading that leads to the beneficial effect observed in MRL/lpr mice after treatment with the phosphorylated peptide 131-151.
METHODS: Peripheral blood lymphocytes (PBLs) from both unprimed MRL/lpr mice and immunized BALB/c mice were tested for their ability to proliferate ex vivo in response to 18 overlapping peptides of the U1-70K spliceosomal protein, using assays for lymphocyte proliferation and secretion of interleukin-2.
RESULTS: The proliferative response to peptides of the U1-70K protein evolved rapidly in MRL/lpr mice tested at different ages. At least 5 peptides were recognized by PBLs from 8-week-old autoimmune mice, whereas a different peptide was recognized by PBLs from MRL/lpr mice at 12 weeks of age. At 15 weeks, the proliferative response was weak or negative when assessed with any of the test peptides. At least 2 major peptides recognized by MRL/lpr PBLs were also recognized by PBLs generated in the BALB/c mice primed with peptide 131-151. We further demonstrated that, in preautoimmune MRL/lpr mice, repeated administration of phosphorylated peptide 131-151 (called P140), which was shown previously to be protective, transiently abolished T cell intramolecular spreading to other regions of the 70K protein.
CONCLUSION: This is the first study to demonstrate that intramolecular T cell spreading effectively occurs in MRL/lpr mice with lupus, and that region 131-151 is important in the cascade of events observed in the murine lupus response. This sequence might originate a mechanism of tolerance spreading that leads to the beneficial effect observed in MRL/lpr mice after treatment with the phosphorylated peptide 131-151.
