Sarin A, Nakajima H, Henkart P A
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
J Immunol. 1995 Jun 1;154(11):5806-12.
Several cysteine and serine protease inhibitors previously shown to block TCR-induced death of 2B4 T hybridoma cells were tested for their ability to block various T lymphocyte apoptotic death systems. TCR-induced death of both peripheral CD4+ and CD8+ T cell blasts was inhibited similarly to the hybridoma, but cell death in these cells induced by anti-Fas, gamma-irradiation, etoposide, or extracellular ATP was not blocked. For T cell lines, cell death induced by CTL or by IL-2 withdrawal was also not inhibited. TCR-induced death of immature CD+8+ thymocytes triggered by culture on immobilized anti-CD3 was not blocked by these protease inhibitors, whereas similar death induced in the resting CD4+8- thymocyte subset under these conditions was inhibited similarly to the T cell blasts. TCR-induced proliferation of the latter subset was modest in the absence of exogeneous IL-2, but was enhanced two- to fourfold by the protease inhibitors. These results show that a protease-dependent death pathway can be triggered by the TCR in mature T cells; similar protease-dependent steps are not common to the TCR-triggered activation pathway or other apoptotic death pathways in these cells.
先前已证明几种半胱氨酸和丝氨酸蛋白酶抑制剂可阻断TCR诱导的2B4 T杂交瘤细胞死亡，现对其阻断各种T淋巴细胞凋亡死亡系统的能力进行了测试。TCR诱导的外周CD4+和CD8+ T细胞母细胞死亡与杂交瘤细胞类似受到抑制，但这些细胞因抗Fas、γ射线照射、依托泊苷或细胞外ATP诱导的细胞死亡未被阻断。对于T细胞系，CTL诱导的或IL-2撤除诱导的细胞死亡也未受到抑制。固定化抗CD3培养触发的未成熟CD8+胸腺细胞的TCR诱导死亡未被这些蛋白酶抑制剂阻断，而在这些条件下静止CD4+8-胸腺细胞亚群诱导的类似死亡与T细胞母细胞类似受到抑制。在无外源性IL-2的情况下，后者亚群的TCR诱导增殖适度，但蛋白酶抑制剂可使其增强两到四倍。这些结果表明，成熟T细胞中的TCR可触发蛋白酶依赖性死亡途径；这些细胞中TCR触发的激活途径或其他凋亡死亡途径并不常见类似的蛋白酶依赖性步骤。
