Wesselborg S, Janssen O, Kabelitz D
Institute of Immunology, University of Heidelberg, Germany.
J Immunol. 1993 May 15;150(10):4338-45.
Signaling via the CD3/TCR complex induces programmed cell death (apoptosis) in immature thymocytes and transformed T lymphocytes (hybridomas or leukemic cells). Accumulating evidence indicates, however, that apoptosis can be triggered also in mature peripheral T cells. Here we show that a significant fraction of cells of a given IL-2-dependent TCR-alpha beta + clone or polyclonal short term line is killed when cultured for 20 h in the presence of PHA, anti-CD3 (OKT3), or anti-TCR (BMA031) mAb. Apoptosis can be triggered by these stimuli in CD4+, CD8+, and CD4-CD8- (double-negative) TCR-alpha beta+ clones. Activation-driven cell death (as quantified by propidium iodide staining and FACS analysis) is associated with fragmentation of DNA into oligonucleosomal bands of approximately 200 bp. Although freshly isolated peripheral blood T cells are largely resistant to apoptosis, the sensitivity to anti-CD3/TCR mAb or PHA-triggered cell death gradually increases upon activation and IL-2-dependent culture of T cells, and reaches a plateau level after 15 to 20 days. These data indicate that stimuli that activate resting T cells initiate death by apoptosis in activated T cells. The implications of these results for the regulation of cellular immune responses and the establishment of peripheral tolerance will be discussed.
通过CD3/TCR复合体发出的信号可诱导未成熟胸腺细胞和转化的T淋巴细胞（杂交瘤细胞或白血病细胞）发生程序性细胞死亡（凋亡）。然而，越来越多的证据表明，成熟外周T细胞也可被触发凋亡。在此我们表明，当在PHA、抗CD3（OKT3）或抗TCR（BMA031）单克隆抗体存在的情况下培养20小时时，给定的依赖白细胞介素-2的TCR-αβ +克隆或多克隆短期细胞系中的相当一部分细胞会被杀死。这些刺激可在CD4 +、CD8 +和CD4 - CD8 -（双阴性）TCR-αβ +克隆中触发凋亡。激活驱动的细胞死亡（通过碘化丙啶染色和流式细胞术分析定量）与DNA断裂成约200 bp的寡核小体条带有关。尽管新鲜分离的外周血T细胞对凋亡具有很大抗性，但在T细胞激活和依赖白细胞介素-2的培养后，其对抗CD3/TCR单克隆抗体或PHA触发的细胞死亡的敏感性会逐渐增加，并在15至20天后达到平台水平。这些数据表明，激活静止T细胞的刺激会在活化的T细胞中引发凋亡死亡。将讨论这些结果对细胞免疫反应调节和外周耐受性建立的意义。
