Young J D, Clark W R, Liu C C, Cohn Z A
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York 10021.
J Exp Med. 1987 Dec 1;166(6):1894-9. doi: 10.1084/jem.166.6.1894.
Cytotoxic T lymphocytes have been thought to lyse cellular targets in the past by a calcium-dependent pathway. This notion was recently supported by the identification and purification of a pore-forming protein (perforin) from the granules of these cell types. Here, we show that perforin is absent from a number of cell lines that nevertheless display vigorous cytolytic activity toward target cells. The cytotoxic activity of eight murine CTL lines is completely or partially retained in the absence of calcium. The calcium-independent lytic activity is associated with two subcellular fraction peaks isolated by Percoll gradient centrifugation, e.g., a heavy density band migrating with granule markers and a lighter band corresponding to free cytosolic material. These results suggest a complex picture of lymphocyte-mediated killing involving probably multiple mechanisms and mediators that may operate in concert or independently in the delivery of the lethal hit.
过去一直认为细胞毒性T淋巴细胞通过钙依赖途径裂解细胞靶标。最近，从这些细胞类型的颗粒中鉴定和纯化出一种成孔蛋白（穿孔素），这一观点得到了支持。在此，我们表明，许多细胞系虽对靶细胞具有强烈的细胞溶解活性，但却不存在穿孔素。在无钙的情况下，8个小鼠CTL系的细胞毒性活性完全或部分得以保留。不依赖钙的溶解活性与通过Percoll梯度离心分离出的两个亚细胞组分峰相关，例如，一个与颗粒标记物一起迁移的高密度带和一个对应于游离胞质物质的较浅带。这些结果提示淋巴细胞介导杀伤的情况较为复杂，可能涉及多种机制和介质，它们在传递致命一击时可能协同或独立发挥作用。
