Phorbol ester and calcium ionophore can replace TCR signals that induce positive selection of CD4 T cells.
Positive selection of immature thymocytes is a developmental process in which TCR ligation by low avidity interaction induces the generation of mature T cells. However, biochemical signals that can induce positive selection have been unclear. By using TCR-alpha beta- mutant thymus cultures, the present study shows that direct stimulation of intracellular signals by PMA and calcium ionophore ionomycin can induce the generation of mature CD4+8- T cells, bypassing TCR-induced positive selection signals. Interestingly, the concentrations of phorbol ester that induced positive selection were more restricted than those that induced mature T cell activation. Moreover, the combination of phorbol ester and ionomycin restored the generation of CD4+8- T cells in class II MHC- thymus cultures, but did not induce the generation of CD4-8+ T cells in class I MHC- thymus cultures. These results identify that the combination of protein kinase C activation and calcium elevation is the biochemical signal that can induce positive selection of CD4+ T cells.
Takahama
Y
Y
Department of Immunology, University of Tsukuba, Japan.
Nakauchi
H
H
D000818:Animals; D000831:Animals, Newborn; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D017637:Clonal Deletion / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D015759:Ionomycin / Q000494:pharmacology*; D007476:Ionophores / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D011493:Protein Kinase C / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000172:deficiency / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013950:Thymus Gland / Q000166:cytology
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007476:Ionophores; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015759:Ionomycin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate