Development of mature CD8+ thymocytes: selection rather than instruction?
The role of major histocompatibility complex (MHC) molecules in T cell differentiation was investigated by comparison of thymocyte subpopulations in wild-type mice and beta 2-microglobulin (beta 2M) mutant mice deficient in MHC class I expression and mature CD8+ cells. On the basis of surface markers, glucocorticoid resistance, in vitro differentiation capacity, and absence in beta 2 M-l- mice, CD4intermediateCD8hi cells with high expression of alpha beta T cell receptor (TCR alpha beta) were identified as having been positively selected by MHC class I for development into mature CD8+ T cells. Activated CD4intCD8hi cells bearing intermediate rather than high amounts of TCR were present in both wild-type and beta 2M-l- animals. These data suggest that recognition of MHC class I molecules is required for full maturation to CD8+ T cells, but not for receptor-initiated commitment to the CD8+ lineage, consistent with a stochastic (selection) model of thymocyte development.
van Meerwijk
J P
JP
Lymphocyte Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Germain
R N
RN
D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis*; D002454:Cell Differentiation; D003907:Dexamethasone / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003907:Dexamethasone