Evidence for a stochastic mechanism in the differentiation of mature subsets of T lymphocytes.
Thymocytes that coexpress the CD4 and CD8 glycoproteins differentiate into mature CD4+ helper or CD8+ cytotoxic cells depending on whether their antigen receptors are specific for MHC class II or class I molecules, respectively. The mechanism of this decision process was investigated in mice whose T cell development was biased toward the class II-specific lineage. We found that constitutive expression of CD4 allows a developmentally arrested population of thymocytes that have mismatched class II-specific TCRs and the CD8 coreceptor to be rescued and to acquire a cytotoxic phenotype. This result is consistent with a two-step process of thymocyte maturation, in which there is stochastic down-regulation of either CD4 or CD8 and subsequent selection based on the ability of the TCR and remaining coreceptor to engage the same MHC molecule.
Davis
C B
CB
Department of Microbiology and Immunology, University of California, San Francisco 94143-0414.
Killeen
N
N
Crooks
M E
ME
Raulet
D
D
Littman
D R
DR
D000818:Animals; D015704:CD4 Antigens / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D016827:CD8 Antigens / Q000502:physiology*; D002454:Cell Differentiation; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013269:Stochastic Processes; D016176:T-Lymphocyte Subsets / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology; D001613:beta 2-Microglobulin / Q000172:deficiency
D015704:CD4 Antigens; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D001613:beta 2-Microglobulin