Nakayama T, Samelson L E, Nakayama Y, Munitz T I, Sheard M, June C H, Singer A
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):9949-53. doi: 10.1073/pnas.88.22.9949.
During thymic selection of the developing T-cell repertoire, the fate of individual CD4+CD8+ thymocytes is determined by the specificity of the T-cell antigen receptors (TCRs) they express. Paradoxically, most CD4+CD8+ thymocytes express few TCR molecules, and those they express are essentially incapable of transducing intracellular signals as measured by intracellular calcium mobilization. However, both TCR number and calcium-signaling capability are significantly induced in CD4+CD8+ thymocytes when the cells are released from intrathymic inhibitory signals that are mediated by their CD4 molecules. Here, the response to ligand engagement of TCR on "induced" CD4+CD8+ thymocytes that have been released from CD4-mediated inhibition was examined and was found to result in internalization of surface TCR complexes and rephosphorylation of zeta chains of the TCR complex. In addition, a proportion of induced CD4+CD8+ thymocytes were found to fragment their DNA upon ligand engagement. Thus, this study describes early events in immature CD4+CD8+ thymocytes resulting from TCR-mediated signals.
在发育中的T细胞库进行胸腺选择期间，单个CD4⁺CD8⁺胸腺细胞的命运由它们所表达的T细胞抗原受体（TCR）的特异性决定。矛盾的是，大多数CD4⁺CD8⁺胸腺细胞表达的TCR分子很少，而且通过细胞内钙动员检测发现，它们所表达的TCR基本上无法转导细胞内信号。然而，当细胞从由其CD4分子介导的胸腺内抑制信号中释放出来时，CD4⁺CD8⁺胸腺细胞中的TCR数量和钙信号传导能力都会显著诱导增加。在此，研究人员检测了从CD4介导的抑制中释放出来的“诱导型”CD4⁺CD8⁺胸腺细胞对TCR配体结合的反应，发现这会导致表面TCR复合物内化以及TCR复合物ζ链的重新磷酸化。此外，研究人员发现一部分诱导型CD4⁺CD8⁺胸腺细胞在配体结合后会使其DNA片段化。因此，本研究描述了由TCR介导的信号在未成熟CD4⁺CD8⁺胸腺细胞中引发的早期事件。
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