Shi Y F, Szalay M G, Paskar L, Sahai B M, Boyer M, Singh B, Green D R
Department of Immunology, University of Alberta, Edmonton, Canada.
J Immunol. 1990 May 1;144(9):3326-33.
Some T cell hybridomas, upon activation via the TCR, rapidly undergo cell death. In this paper, we demonstrate that this activation-induced cell death (AICD) is accompanied by morphologic changes seen at the electron and light microscopy levels. The most striking changes are an extensive condensation of the chromatin and formation of membrane blebs. In addition to the morphologic changes, a significant portion of genomic DNA is broken at an interval of approximately 200 bp, producing a ladder of oligonucleosome-sized fragments after gel electrophoresis. Taken together, these observations indicate that AICD proceeds via apoptosis, or programmed cell death. This is additionally supported by the observation that AICD-associated phenomena are at least partially inhibited by cycloheximide or actinomycin D. Curiously, AICD and its associated DNA fragmentation are completely inhibited by aurintricarboxylic acid, a known nuclease inhibitor. The possible relationship between AICD in vitro, and the negative selection process (wherein selection may proceed via AICD of developing, autoreactive thymocytes) is discussed.
一些T细胞杂交瘤通过TCR激活后会迅速发生细胞死亡。在本文中,我们证明这种激活诱导的细胞死亡(AICD)伴随着在电子显微镜和光学显微镜水平上观察到的形态学变化。最显著的变化是染色质广泛凝聚和膜泡形成。除了形态学变化外,相当一部分基因组DNA以约200 bp的间隔断裂,在凝胶电泳后产生寡核小体大小片段的梯状条带。综上所述,这些观察结果表明AICD通过凋亡或程序性细胞死亡进行。环己酰亚胺或放线菌素D至少部分抑制AICD相关现象这一观察结果进一步支持了这一点。奇怪的是,金精三羧酸(一种已知的核酸酶抑制剂)完全抑制AICD及其相关的DNA片段化。本文讨论了体外AICD与阴性选择过程(其中选择可能通过发育中的自身反应性胸腺细胞的AICD进行)之间的可能关系。