Lee M R, Liou M L, Liou M L, Yang Y F, Lai M Z
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, R.O.C.
J Immunol. 1993 Nov 15;151(10):5208-17.
Activation of T cell hybridomas through their TCR leads to secretion of IL-2, inhibition of proliferation, and apoptosis. The identification of various inhibitors that prevent activation-induced T cell death (AICD) has helped identify several essential events in apoptosis. For example, inhibition of AICD by dexamethasone indicates a connection between these two programmed death pathways. In this study, we have investigated the interaction between the cAMP signal transduction pathway and the activation- or glucocorticoid-induced cell death. cAMP induced DNA fragmentation in thymocytes. T cell hybridomas displayed different sensitivity to cAMP. Regardless of its cAMP sensitivity, programmed cell death promoted by anti-CD3 or Ag in hybridoma was prevented by the presence of cAMP analogs. In contrast, cAMP had no effect on glucocorticoid-induced T cell death. The inhibitory effect of cAMP on AICD was unlikely to be due to quenching of T cell activation signals, because cAMP added 1 h after T cell activation could still prevent cell death. In addition, the increased binding of AP-1, NF-AT, and NF-kappa B during T cell activation was not significantly affected by cAMP. The presence of the inhibitory cAMP-mediated signals, together with the glucocorticoid-induced pathway, suggest there are at least two distinct mechanisms regulating AICD in immature lymphocytes.
通过T细胞杂交瘤的TCR激活会导致白细胞介素-2的分泌、增殖抑制和细胞凋亡。多种可防止激活诱导的T细胞死亡（AICD）的抑制剂的鉴定，有助于确定细胞凋亡中的几个关键事件。例如，地塞米松对AICD的抑制表明这两种程序性死亡途径之间存在联系。在本研究中，我们研究了cAMP信号转导途径与激活或糖皮质激素诱导的细胞死亡之间的相互作用。cAMP诱导胸腺细胞中的DNA片段化。T细胞杂交瘤对cAMP表现出不同的敏感性。无论其对cAMP的敏感性如何，杂交瘤中由抗CD3或抗原促进的程序性细胞死亡都可被cAMP类似物的存在所阻止。相比之下，cAMP对糖皮质激素诱导的T细胞死亡没有影响。cAMP对AICD的抑制作用不太可能是由于T细胞激活信号的淬灭，因为在T细胞激活1小时后添加cAMP仍可防止细胞死亡。此外，T细胞激活过程中AP-1、NF-AT和NF-κB结合的增加并未受到cAMP的显著影响。抑制性cAMP介导的信号的存在，与糖皮质激素诱导的途径一起，表明至少有两种不同的机制调节未成熟淋巴细胞中的AICD。
