Kuwano K, Akashi A, Arai S
Department of Microbiology, Kurume University School of Medicine, Fukuoka, Japan.
Cell Immunol. 1998 May 1;185(2):114-22. doi: 10.1006/cimm.1998.1289.
T cell receptor (TCR) occupancy in the absence of a costimulatory signal transforms T helper (Th) cells or cytotoxic T lymphocytes (CTL) into a state of anergy. The anergic T cells are unable to produce cytokines; nevertheless, they maintain their killing activity. We investigated the mechanisms through which anergic CTL causes lysis of target cells. Treatment of a CTL clone with phorbol myristate acetate and calcium ionophore A23187 (P/A) transformed these cells to anergic cells. While the anergic CTL clones failed to secrete TNF-alpha in the culture supernatant, they were still able to kill antigen-specific target cells via a granule exocytosis-mediated pathway. This was evident by the synthesis of perforin mRNA and release of N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester esterase by these cells. The anergic CTL clone also showed a low degree of Fas-mediated lysis of normal target cells. In addition, we generated anergic bulk CTL by treatment with P/A and observed that the anergic bulk CTL failed to produce TNF upon antigen stimulation, but retained target killing activity via a granule exocytosis mechanism. Our results suggest that the killing mechanisms of anergic CTL are mediated to a large extent by a granule exocytosis-mediated pathway.
在缺乏共刺激信号的情况下，T细胞受体（TCR）占据会将辅助性T细胞（Th）或细胞毒性T淋巴细胞（CTL）转变为无反应状态。无反应性T细胞无法产生细胞因子；然而，它们仍保持杀伤活性。我们研究了无反应性CTL导致靶细胞裂解的机制。用佛波酯肉豆蔻酸酯和钙离子载体A23187（P/A）处理CTL克隆会将这些细胞转变为无反应性细胞。虽然无反应性CTL克隆未能在培养上清液中分泌肿瘤坏死因子-α（TNF-α），但它们仍能够通过颗粒胞吐介导的途径杀伤抗原特异性靶细胞。这些细胞合成穿孔素mRNA并释放N-α-苄氧羰基-L-赖氨酸硫代苄酯酯酶就证明了这一点。无反应性CTL克隆对正常靶细胞也表现出低程度的Fas介导的裂解。此外，我们通过用P/A处理产生了无反应性大量CTL，并观察到无反应性大量CTL在抗原刺激时未能产生TNF，但通过颗粒胞吐机制保留了靶细胞杀伤活性。我们的结果表明，无反应性CTL的杀伤机制在很大程度上是由颗粒胞吐介导的途径介导的。
