Wesselborg S, Kabelitz D
Institute of Immunology, University of Heidelberg, Germany.
Cell Immunol. 1993 Apr 15;148(1):234-41. doi: 10.1006/cimm.1993.1106.
Signaling via the CD3/T cell receptor complex induces programmed cell death (apoptosis) in IL-2-dependent human T lymphocytes. We have investigated the time course kinetics of the induction of programmed cell death in cloned CD4+ T cells. Morphological changes (cell shrinkage) were noted by flow cytometry as early as 3 hr after stimulation of clone cells with ionomycin, PHA, or anti-T cell receptor antibody BMA 031. Fragmentation of DNA became visible 3 hr after ionomycin stimulation, and 5 hr after PHA or BMA 031 stimulation, and peaked after 8 to 24 hr. Significant cell death (as revealed by flow cytometry analysis of propidium iodide-positive cells) was detected 5 hr after ionomycin treatment and 10 hr after PHA or BMA 031 treatment. With all three stimuli, maximal cell death was recorded after 16 to 18 hr. Taken together, our data indicate that the activation-induced death of mature human T cells is a rapid event which is completed within 18 hr. Induction of DNA fragmentation is preceded by the reduction of cell size which can be readily examined by flow cytometry.
通过CD3/T细胞受体复合物发出的信号可诱导白细胞介素-2依赖的人T淋巴细胞发生程序性细胞死亡（凋亡）。我们研究了克隆的CD4+ T细胞中程序性细胞死亡诱导的时间进程动力学。早在用离子霉素、PHA或抗T细胞受体抗体BMA 031刺激克隆细胞3小时后，通过流式细胞术就可观察到形态学变化（细胞收缩）。离子霉素刺激3小时后，PHA或BMA 031刺激5小时后，DNA片段化可见，并在8至24小时后达到峰值。离子霉素处理5小时后以及PHA或BMA 031处理10小时后，检测到显著的细胞死亡（通过碘化丙啶阳性细胞的流式细胞术分析显示）。使用所有三种刺激物，在16至18小时后记录到最大细胞死亡。综上所述，我们的数据表明，成熟人T细胞的激活诱导死亡是一个快速事件，在18小时内完成。DNA片段化的诱导之前是细胞大小的减小，这可以通过流式细胞术轻松检测。
