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 fo...

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Bibliographic Details
Published in:Cellular immunology 1998-01, Vol.183 (1), p.70-79
Main Authors: DiMolfetto, L, Neal, H A, Wu, A, Reilly, C, Lo, D
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic
AIDS/HIV
Animals
B-Lymphocytes - metabolism
Cell Count
Cells, Cultured
Dendritic Cells - metabolism
Female
Gene Expression
Histocompatibility Antigens Class II - genetics
Histocompatibility Antigens Class II - immunology
Interferon-gamma - immunology
Interleukin-4 - immunology
Ligands
Lymph Nodes - immunology
Lymphocyte Activation
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Receptors, Antigen, T-Cell - immunology
T-Lymphocytes - immunology
Th1 Cells - immunology
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Summary: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.
ISSN:0008-8749
1090-2163
DOI:10.1006/cimm.1997.1231