Takahama Y, Nakauchi H
Department of Immunology, University of Tsukuba, Japan.
J Immunol. 1996 Aug 15;157(4):1508-13.
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.
未成熟胸腺细胞的阳性选择是一个发育过程，其中通过低亲和力相互作用的TCR连接诱导成熟T细胞的产生。然而，能够诱导阳性选择的生化信号尚不清楚。通过使用TCR-αβ-突变胸腺培养物，本研究表明，佛波酯（PMA）和钙离子载体离子霉素对细胞内信号的直接刺激可以诱导成熟CD4+8-T细胞的产生，绕过TCR诱导的阳性选择信号。有趣的是，诱导阳性选择的佛波酯浓度比诱导成熟T细胞活化的浓度限制更严格。此外，佛波酯和离子霉素的组合恢复了II类MHC-胸腺培养物中CD4+8-T细胞的产生，但在I类MHC-胸腺培养物中未诱导CD4-8+T细胞的产生。这些结果表明，蛋白激酶C激活和钙升高的组合是能够诱导CD4+T细胞阳性选择的生化信号。
