Duke R C, Sellins K S, Cohen J J
Department of Microbiology and Immunology, University of Colorado School of Medicine, Denver 80262.
J Immunol. 1988 Oct 1;141(7):2191-4.
When target cells are exposed to CTL, they very quickly sustain nuclear damage, including DNA cleavage, and then they lyse. Nuclear damage of this type is not seen when cells are killed by antibody and C. The role of nuclear damage in the T cell-mediated killing process as well as the mechanism by which the killer cell induces this damage are unknown; however, accumulating evidence suggests that cytolysis may depend on induction of nuclear damage. The exocytosed contents of CTL granules are thought by many workers to mediate target cell lysis. We have now determined whether lytic granules also induce nuclear damage (DNA fragmentation) in cells which they lyse. They do not. In addition, no DNA fragmentation was detected in nuclei incubated with lytic granules or activated CTL. In summary, our results suggest that target cell DNA fragmentation induced by CTL is mediated neither by lytic granules nor by a CTL-derived endonuclease and support the view that the target cell is itself responsible for the internal damage it sustains.
当靶细胞暴露于细胞毒性T淋巴细胞（CTL）时，它们会很快遭受核损伤，包括DNA裂解，然后发生裂解。当细胞被抗体和补体（C）杀死时，不会出现这种类型的核损伤。核损伤在T细胞介导的杀伤过程中的作用以及杀伤细胞诱导这种损伤的机制尚不清楚；然而，越来越多的证据表明细胞溶解可能依赖于核损伤的诱导。许多研究人员认为，CTL颗粒胞吐的内容物介导了靶细胞的裂解。我们现在已经确定裂解颗粒是否也会在它们裂解的细胞中诱导核损伤（DNA片段化）。结果表明它们不会。此外，在用裂解颗粒或活化的CTL孵育的细胞核中未检测到DNA片段化。总之，我们的结果表明，CTL诱导的靶细胞DNA片段化既不是由裂解颗粒介导的，也不是由CTL衍生的核酸内切酶介导的，这支持了靶细胞自身应对其所遭受的内部损伤负责的观点。
