Waterhouse Nigel J, Clarke Chris J P, Sedelies Karin A, Teng Michele W, Trapani Joseph A
Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett St, Melbourne, Vic. 8006, Australia.
Biochem Pharmacol. 2004 Sep 15;68(6):1033-40. doi: 10.1016/j.bcp.2004.05.043.
Most mammalian cells are constantly threatened by viral infection and oncogenic transformation. To maintain healthy function of organs and tissues it is critical that afflicted cells are efficiently detected and removed. Cytotoxic lymphocytes (CL) are chiefly responsible for efficiently seeking out and eliminating damaged or infected cells. It is known that CLs must specifically recognize and bind to their targets, but the molecular events that occur within the target cell that lead to its death are still poorly understood. The two main processes initiated by CLs to induce target cell death are mediated by ligation of surface receptors or release of toxic proteins from secretory granules (granule exocytosis) of the CL. Here we review some of the key findings that have defined our knowledge of the granule exocytosis-mediated pathways to CL-mediated killing and discuss recent insights that challenge conventional views in the important area of CL effector function.
大多数哺乳动物细胞经常受到病毒感染和致癌转化的威胁。为维持器官和组织的健康功能，高效检测和清除受影响的细胞至关重要。细胞毒性淋巴细胞（CL）主要负责高效地寻找和清除受损或感染的细胞。已知CL必须特异性识别并结合其靶标，但靶细胞内导致其死亡的分子事件仍知之甚少。CL诱导靶细胞死亡引发的两个主要过程是由表面受体的连接或CL分泌颗粒（颗粒胞吐作用）释放有毒蛋白质介导的。在此，我们回顾了一些关键发现，这些发现界定了我们对颗粒胞吐作用介导的CL介导杀伤途径的认识，并讨论了最近在CL效应器功能这一重要领域挑战传统观点的见解。
