Lancki D W, Weiss A, Fitch F W
J Immunol. 1987 Jun 1;138(11):3646-53.
Cloned murine cytolytic T lymphocytes (CTL) having defined specificity were triggered by the phorbol ester together with a calcium ionophore (either A23187 or Ionomycin) to lyse syngeneic or third party target cells efficiently. Neither phorbol 12-myristate 13-acetate (PMA) nor calcium ionophore alone induced efficient lysis. The characteristics of the lytic process induced by these signals are similar to those of antigen-specific or lectin-facilitated lysis by CTL. Lysis is calcium and temperature dependent and shows kinetics which are not grossly different from lysis mediated via the antigen receptor. Two helper T lymphocyte clones were not induced to lyse efficiently EL-4 target cells by concanavalin A or PMA + ionophore. Triggering of lysis induced with PMA plus ionophore by the CTL clone L3 differed from antigen-mediated lysis in specificity and in the susceptibility to inhibition by cytochalasin B. Properties of the target cell determine which cell surface associative recognition structures are important in the efficient lysis of these cells. Anti-LFA-1 monoclonal antibodies inhibited efficiently both antigen-mediated and PMA + ionophore-induced lysis of P-815 or EL-4 target cells which are of hematopoietic origin. However, anti-LFA-1 antibodies do not inhibit antigen-mediated, lectin-facilitated, or PMA + Ionomycin-induced CTL cytolysis of target cells derived from the L cell fibroblast line. We conclude that two intracellular signals, which can be provided by the combination of PMA + ionophore, are required for efficient lysis by antigen-specific murine CTL clones. When the T cell receptor for antigen is bypassed using PMA + ionophore to trigger lysis, we show that Lyt-2 and LFA-1 molecules may be required for efficient lysis. These associative recognition structures appear to play an important role in postactivation steps leading to efficient delivery of the lethal hit to the target cell.
具有明确特异性的克隆化小鼠细胞毒性T淋巴细胞（CTL），在佛波酯与钙离子载体（A23187或离子霉素）共同作用下，能有效裂解同基因或第三方靶细胞。单独的佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯（PMA）或钙离子载体均不能诱导有效裂解。这些信号诱导的裂解过程的特征，与CTL的抗原特异性或凝集素促进的裂解过程相似。裂解依赖于钙离子和温度，其动力学与通过抗原受体介导的裂解并无显著差异。两种辅助性T淋巴细胞克隆，在刀豆球蛋白A或PMA + 离子载体作用下，未被诱导有效裂解EL - 4靶细胞。CTL克隆L3由PMA加离子载体诱导的裂解触发，在特异性和对细胞松弛素B抑制的敏感性方面，与抗原介导的裂解不同。靶细胞的特性决定了哪些细胞表面联合识别结构，对于这些细胞的有效裂解至关重要。抗LFA - 1单克隆抗体能有效抑制造血来源的P - 815或EL - 4靶细胞的抗原介导和PMA + 离子载体诱导的裂解。然而，抗LFA - 1抗体并不抑制来自L细胞成纤维细胞系的靶细胞的抗原介导、凝集素促进或PMA + 离子霉素诱导的CTL细胞溶解。我们得出结论，抗原特异性小鼠CTL克隆有效裂解需要两种细胞内信号，这两种信号可由PMA + 离子载体组合提供。当使用PMA + 离子载体绕过抗原的T细胞受体来触发裂解时，我们发现Lyt - 2和LFA - 1分子可能是有效裂解所必需的。这些联合识别结构似乎在导致向靶细胞有效传递致命一击的激活后步骤中发挥重要作用。
