Smyth M J, Trapani J A
Cellular Cytotoxicity Laboratory, Austin Research Institute, Heidelberg, Australia.
Immunol Today. 1995 Apr;16(4):202-6. doi: 10.1016/0167-5699(95)80122-7.
Cytotoxic lymphocytes mediate immunity against viruses and surveillance against neoplastic transformation. They kill target cells by multiple mechanisms, but utilize a pore-forming protein, perforin, and a family of serine proteinases as their principal means of inflicting cell death. Recent studies have demonstrated that perforin and serine proteinases synergistically trigger an endogenous pathway of apoptosis resulting in dissolution of the target cell nuclear membrane and DNA fragmentation. These changes may be secondary to inappropriate activation of p34cdc2 kinase and the subsequent derangement of cell cycle control. As discussed by Mark Smyth and Joseph Trapani, the immediate molecular targets of perforin/granzyme-mediated apoptosis are still unclear, though candidate molecules with homology to cell death gene products from primitive organisms are currently under close scrutiny.
细胞毒性淋巴细胞介导针对病毒的免疫以及对肿瘤转化的监测。它们通过多种机制杀死靶细胞，但主要利用一种成孔蛋白——穿孔素和一族丝氨酸蛋白酶来导致细胞死亡。最近的研究表明，穿孔素和丝氨酸蛋白酶协同触发内源性凋亡途径，导致靶细胞核膜溶解和DNA片段化。这些变化可能继发于p34cdc2激酶的不适当激活以及随后细胞周期调控的紊乱。正如马克·史密斯和约瑟夫·特拉帕尼所讨论的，穿孔素/颗粒酶介导的凋亡的直接分子靶点仍不清楚，尽管目前与原始生物细胞死亡基因产物具有同源性的候选分子正受到密切关注。
