Tirosh R, Berke G
Cell Immunol. 1985 Oct 1;95(1):113-23. doi: 10.1016/0008-8749(85)90300-4.
Delivery of the lethal hit signal to target cells (TC) by cytolytic T lymphocyte (CTL) has traditionally been considered strictly dependent upon the presence of external Ca2+ [( Ca2+]ext) in the medium, but neither the role of Ca2+ nor its site of action (effector or target) have been known. We have observed that in different CTL/TC systems the requirement for [Ca2+]ext varies, depending on the target. Some TC, like leukemia L1210, are strictly dependent on [Ca2+]ext for lysis while others, like EL4 (and P815), are not. It is therefore suggested that, where required, [Ca2+]ext exerts its effect(s) on the TC and not the CTL. In support of this conclusion are experiments showing that effector cells cytolytic to certain TC in the absence of [Ca2+]ext, require [Ca2+]ext when used themselves as TC of other effectors. Verapamil, a Ca2+-channel blocker, inhibits the lysis of L1210 but not of EL4 cells, suggesting involvement of Ca2+ flux into L1210 target cells and, if at all involved, Ca2+ mobilization from internal stores in EL4. The different lytic susceptibility of the two TC to the Ca2+ ionophore A23187, in the presence and absence of [Ca2+]ext, correlated with their responses to CTL. It suggests Ca2+ influx into both types of TC in the presence of [Ca2+]ext and its release from internal stores in the lysis of EL4 but not L1210 in the absence of [Ca2+]ext. In view of these results indicating that the target is the site of Ca2+ action, we propose that CTL induce a Ca2+-regulated activation of the TC leading to its lysis.
传统上认为，细胞毒性T淋巴细胞（CTL）向靶细胞（TC）传递致死性打击信号严格依赖于培养基中存在外部钙离子（[Ca2+]ext），但钙离子的作用及其作用位点（效应细胞或靶细胞）均不清楚。我们观察到，在不同的CTL/TC系统中，对[Ca2+]ext的需求各不相同，这取决于靶细胞。一些靶细胞，如白血病L1210，其裂解严格依赖于[Ca2+]ext，而其他靶细胞，如EL4（和P815）则不然。因此表明，在需要时，[Ca2+]ext对靶细胞而非CTL发挥作用。支持这一结论的实验表明，在没有[Ca2+]ext的情况下，对某些靶细胞具有细胞毒性的效应细胞，当自身作为其他效应细胞的靶细胞时，则需要[Ca2+]ext。维拉帕米是一种钙通道阻滞剂，它能抑制L1210细胞的裂解，但不能抑制EL4细胞的裂解，这表明钙离子流入L1210靶细胞参与其中，而对于EL4细胞，如果有参与的话，钙离子是从内部储存库中动员出来的。在有和没有[Ca2+]ext的情况下，两种靶细胞对钙离子载体A23187的不同裂解敏感性与它们对CTL的反应相关。这表明在有[Ca2+]ext存在时，钙离子流入两种类型的靶细胞，而在没有[Ca2+]ext的情况下，EL4细胞裂解时钙离子从内部储存库释放出来，而L1210细胞则不然。鉴于这些结果表明靶细胞是钙离子的作用位点，我们提出CTL诱导靶细胞的钙离子调节激活，从而导致其裂解。
