Generation of mature T cell populations in the thymus: CD4 or CD8 down-regulation occurs at different stages of thymocyte differentiation.
We have studied the differentiation and repertoire selection during the maturation of CD4+CD8+ (DP) thymocytes into CD4+CD8- (CD4SP) and CD8+CD4- (CD8SP) T cells, in normal mice, mice transgenic for T cell receptor (TcR)-alpha beta restricted by either class I or class II major histocompatibility (MHC), and in mice deficient in class I or class II MHC expression. Our data suggest that mature CD4 and CD8 T cells derive from different pathways of T cell differentiation in the thymus. Thus, interaction of DP thymocytes with MHC class II leads to the immediate down-regulation of CD8, which occurs simultaneously with an increase in TcR expression; DPTcR(lo)HSA(hi) thymocytes mature into a CD4+CD8(lo) TcR(hi)HSA(hi) intermediate population. This cell population generates CD4SP thymocytes, the majority of which are still HSA(hi). In contrast, interaction with MHC class I induces the up-regulation of TcR, which precedes the down-regulation of CD4; DPTcR(lo) generate DPTcR(hi) thymocytes, the majority of which are the committed precursors of CD8SP cells. Further differentiation results in CD4 down-regulation and the transition from DPTcR(hi) into CD8+CD4(lo) TcR(hi)HSA(lo) and +D8SPTcR(hi)HSA- T cells. Since down-regulation of CD4 and CD8 occurs at different stages of thymocyte differentiation, our results do not support a stochastic/selective model of lineage commitment in the thymus.
Marodon
G
G
U.345 INSERM, Necker Institute, Paris, France.
Rocha
B
B
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D016827:CD8 Antigens; D002454:Cell Differentiation; D048429:Cell Size; D015536:Down-Regulation / Q000502:physiology; D005434:Flow Cytometry; D006649:Histocompatibility Antigens / Q000235:genetics; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology*
D016827:CD8 Antigens; D006649:Histocompatibility Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta