Exocytosis of cytolytic granules may not be required for target cell lysis by cytotoxic T-lymphocytes
Exocytosis of cytolytic granules may not be required for target cell lysis by cytotoxic T-lymphocytes
复制标题
细胞毒性 T 淋巴细胞裂解靶细胞可能不需要溶细胞颗粒的胞吐作用
作者：
G. Trenn;H. Takayama;M. Sitkovsky
分泌过程与细胞毒性 T 淋巴细胞 (CTL) 裂解靶细胞的机制有关（参考文献 1,2）。 CTL 和细胞毒性大颗粒淋巴细胞均具有溶细胞颗粒 3,4，其中含有溶细胞分子“穿孔素”3 和“溶细胞素”4；穿孔素和细胞毒性淋巴细胞可以通过孔的膜组装损伤靶细胞3-5。与细胞毒性细胞相关且位于颗粒的蛋白酶的描述支持了细胞毒性淋巴细胞介导的细胞毒性的颗粒胞吐作用模型，并强调了细胞介导的细胞毒性和补体介导的细胞毒性之间的相似性6-14。但最近的实验 15 对裂解颗粒和穿孔素在 CTL ac15,16 中的重要性提出了挑战。在这里，我们报告说，即使细胞外钙的去除消除了溶解颗粒的胞吐作用，CTL 也可以被触发，对靶细胞产生致命的打击。颗粒胞吐作用的解离和致命打击的传递表明，溶细胞颗粒可能不参与 CTL 的靶细胞裂解。
Secretory processes have been implicated in the mechanism of target-cell lysis by cytotoxic T-lymphocytes (CTL) (refs 1,2). Both CTL and cytotoxic large granular lymphocytes have cytolytic granules3,4, containing the cytolytic molecules 'perforin'3 and 'cytolysin'4; perforin and cytotoxic lymphocytes can damage target cells through the membrane assembly of pores3–5. The description of proteases which are cytotoxic cell-associated and granule-located has supported the granule exocytosis model of cytotoxicity mediated by cytotoxic lymphocytes, and has emphasized the similarities between cell-mediated and complement-mediated cytotoxicity6–14. But recent experiments have15 challenged the importance of lytic granules and perforin in CTL ac15,16. Here we report that CTL can be triggered to deliver a lethal hit to target cells even when exocytosis of lytic granules has been abolished by removal of extracellular calcium. This dissociation of exocytosis of granules and delivery of the lethal hit suggests that cytolytic granules may not be involed in target-cell lysis by CTL.