Nishioka W K, Welsh R M
Department of Pathology, University of Massachusetts Medical Center, Worcester 01655.
J Exp Med. 1994 Feb 1;179(2):769-74. doi: 10.1084/jem.179.2.769.
Cytotoxic T lymphocytes (CTL) kill cells by perturbing the target's plasma membrane and by inducing the disintegration of the target cell's DNA into oligonucleosomal fragments, a process characteristic of apoptosis. We show that the DNA fragmentation event is distinct from the membrane lysis event and is dependent on the state of target cell activation or commitment into the mitotic cycle. Quiescent cells were refractory to DNA fragmentation, but not to membrane lysis. Log phase growth, transformation with c-myc, or infection of quiescent G0 targets with herpes simplex virus-1, which induces a competent state for DNA synthesis, all enhanced target cell susceptibility to CTL-induced DNA fragmentation without altering the membrane lysis. These results suggest that G0 cells are resistant to CTL-induced apoptosis, but that entry into G1 or a G1-like state by growth factors, cellular transformation, or DNA virus infection renders them competent to enter the apoptotic pathway(s).
细胞毒性T淋巴细胞（CTL）通过干扰靶细胞的质膜以及诱导靶细胞DNA降解为寡核小体片段来杀伤细胞，这是细胞凋亡的一个特征性过程。我们发现DNA片段化事件与膜裂解事件不同，并且依赖于靶细胞的激活状态或进入有丝分裂周期的状态。静止细胞对DNA片段化具有抗性，但对膜裂解没有抗性。对数期生长、用c-myc转化或用单纯疱疹病毒1感染静止的G0靶细胞（可诱导DNA合成的活性状态），均可增强靶细胞对CTL诱导的DNA片段化的敏感性，而不改变膜裂解。这些结果表明，G0细胞对CTL诱导的细胞凋亡具有抗性，但生长因子、细胞转化或DNA病毒感染使其进入G1期或类似G1期的状态后，它们就有能力进入凋亡途径。
