Human T cells require IL-2 but not G1/S transition to acquire susceptibility to Fas-mediated apoptosis.
Human T cells require IL-2 but not G1/S transition to acquire susceptibility to Fas-mediated apoptosis.
复制标题
人类 T 细胞需要 IL-2 而不是 G1/S 转变才能获得对 Fas 介导的细胞凋亡的敏感性。
作者：
S. Fournel;L. Genestier;É. Robinet;M. Flacher;J. Revillard
Fas配体与Fas之间的相互作用是激活诱导的细胞死亡调控的主要途径，Fas均在活化的T细胞上表达。然而，表达膜Fas的活化T细胞最初对抗Fas诱导的凋亡具有抗性，只有在体外增殖后才变得敏感。由于已知IL-2可调节活化诱导的细胞死亡，我们研究了IL-2对抗fas介导的细胞凋亡的影响。对IL-2通路的干扰包括：1)使用环孢素A或FK506抑制细胞因子合成，2)使用抗IL-2抗体中和IL-2, 3)使用CD25单抗抑制IL-2R结合，4)使用雷帕霉素阻断IL-2R信号传导。我们发现Fas的表达不依赖于IL-2通路，而Fas介导的细胞凋亡在IL-2产生或信号传导抑制剂存在的情况下不会发生。虽然添加rIL-2逆转了环孢素A和FK506的抑制作用，但添加rIL-4、rIL-7或rifn - γ却没有，尽管这些细胞因子诱导细胞周期进入S期。未进入S期的经aphidicolin处理的活化T细胞易发生fas介导的凋亡。因此，fas介导的细胞凋亡是由IL-2产生的信号控制的，这与报道的IL-2或IL-2R缺乏小鼠的细胞凋亡改变一致。
The interaction between Fas ligand and Fas, both expressed on activated T cells, is the major pathway in the regulation of activation-induced cell death. However, activated T cells that express membrane Fas are initially resistant to anti-Fas-induced apoptosis and become susceptible only after proliferation in vitro. Since IL-2 is known to regulate activation-induced cell death, we studied the effect of IL-2 on anti-Fas-mediated apoptosis. Interference with the IL-2 pathway was achieved by 1) inhibition of cytokine synthesis using cyclosporin A or FK506, 2) neutralization of IL-2 by anti-IL-2 Ab, 3) inhibition of binding to IL-2R by CD25 mAb, and 4) blocking of IL-2R signaling by rapamycin. We show that Fas expression is independent of the IL-2 pathway, whereas Fas-mediated apoptosis does not develop in the presence of inhibitors of IL-2 production or signaling. While the addition of rIL-2 reversed the inhibitory effect of cyclosporin A and FK506, the addition of rIL-4, rIL-7, or rIFN-gamma did not, although these cytokines induced progression into the S phase of the cell cycle. Aphidicolin-treated activated T cells that do not progress into the S phase were susceptible to Fas-mediated apoptosis. Therefore, Fas-mediated apoptosis is controlled by signals generated by IL-2 in agreement with the reported alteration of apoptosis in mice deficient in IL-2 or IL-2R.