The density of the class II MHC T cell receptor ligand influences IFN-gamma/IL-4 ratios in immune responses in vivo.
Activation of CD4+ T cells depends on T cell receptor recognition of MHC class II/peptide and on costimulation provided by CD28/B7. It has been shown that different levels of costimulation can influence T helper cell differentiation into Th1 versus Th2 phenotypes. Similar arguments have been made for different levels of peptide/MHC density on antigen-presenting cells, but to date supportive evidence has only come from in vitro studies. Here, using transgenic mice with reduced MHC class II expression on both B cells and dendritic cells, we demonstrate that T helper cell differentiation in vivo is also influenced by the density of expression of MHC class II. Although priming and expansion of antigen-specific T cells were normal in these mice, T cell responses were dominated by the Th1-associated cytokine IFN-gamma, with reduced levels of the Th2 cytokine IL-4 compared to controls. These results provide direct evidence that the efficiency of antigen presentation in vivo can determine effector cell phenotype.
DiMolfetto
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Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
Neal
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Wu
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Reilly
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Lo
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D000276:Adjuvants, Immunologic; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002452:Cell Count; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D008024:Ligands; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
D000276:Adjuvants, Immunologic; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4; D007371:Interferon-gamma