MHC control of CD4+ T cell subset activation.
The present results demonstrate that CD4+ T cells activated in the primary in vivo response to antigen produce distinct patterns of cytokines depending upon the MHC class II haplotype of the responding mice. I-As mice were found to selectively activate IL-2/IFN-gamma-producing CD4+ T cells, whereas I-Ab mice exhibited selective activation of IL-4-producing CD4+ T cells in response to collagen IV. The effector response phenotype was found to correlate with the cytokine phenotype of CD4+ T cells activated in vivo; IL-2/IFN-gamma-producing cells giving rise to proliferative (cell-mediated) responses, IL-4-producing cells leading to secondary IgG (humoral) responses. Together the data support the notion that the outcome of a given immune response (e.g., protection vs. onset, tolerance vs. autoimmunity) may be determined in part by the type of CD4+ T cells initially activated by antigen. Moreover, the present experiments demonstrate for the first time that polymorphism in class II MHC can determine such selective activation of different cytokine-producing CD4+ T cell phenotypes.
Murray
J S
JS
Section of Immunobiology, Howard Hughes Medical Institute Yale University School of Medicine, New Haven, Connecticut 06510.
Madri
J
J
Tite
J
J
Carding
S R
SR
Bottomly
K
K
D000818:Animals; D001685:Biological Factors / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003094:Collagen / Q000276:immunology; D016207:Cytokines; D005260:Female; D005802:Genes, MHC Class II; D007074:Immunoglobulin G / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D014301:Trinitrobenzenes / Q000276:immunology
D001685:Biological Factors; D016207:Cytokines; D007074:Immunoglobulin G; D014301:Trinitrobenzenes; D003094:Collagen