Geisberg M, Dupont B
Laboratory of Human Immunogenetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Int Immunol. 1992 Nov;4(11):1273-81. doi: 10.1093/intimm/4.11.1273.
Antigen-specific cytotoxic killer lymphocytes (CTLs) represent one of the major effector functions of the immune system. It is well established that, as a consequence of TCR recognition of the antigen-bearing target cell, resting T lymphocytes develop into fully active antigen-specific CTLs. In contrast, natural killer (NK) cells are immediately lytic upon contact with an appropriate target cell. The lytic machinery of CTLs and NK cells is thought to include the contents of their cytoplasmic granules, in particular the pore-forming protein perforin. Here we report direct cytolytic activity by resting peripheral CD3+CD8+ T cells as a result of TCR-CD3 binding to the target cell; the murine OKT3 hybridoma (anti-human CD3) was used as a target. The cytotoxicity was more pronounced in the CD8+CD45RO+ population, which contains 'memory' T cells, than in the reciprocal CD8+CD45RA+ subset; CD8+CD4- mature thymocytes were non-cytotoxic. The cytolytic potential of these populations correlated with the presence or absence of perforin. The results demonstrate that the cytolytic machinery of T cells develops post-thymically and can be immediately triggered by TCR-CD3 stimulation.
抗原特异性细胞毒性杀伤淋巴细胞(CTLs)是免疫系统的主要效应功能之一。众所周知,由于TCR识别携带抗原的靶细胞,静止的T淋巴细胞会发育成完全活化的抗原特异性CTLs。相比之下,自然杀伤(NK)细胞与合适的靶细胞接触后会立即产生细胞溶解作用。CTLs和NK细胞的细胞溶解机制被认为包括其细胞质颗粒的内容物,特别是成孔蛋白穿孔素。在此,我们报告了静止外周血CD3+CD8+T细胞因TCR-CD3与靶细胞结合而产生的直接细胞溶解活性;将鼠OKT3杂交瘤(抗人CD3)用作靶细胞。在含有“记忆”T细胞的CD8+CD45RO+群体中,细胞毒性比在相应的CD8+CD45RA+亚群中更明显;CD8+CD4-成熟胸腺细胞无细胞毒性。这些群体的细胞溶解潜能与穿孔素的存在与否相关。结果表明,T细胞的细胞溶解机制在胸腺后发育,并且可以由TCR-CD3刺激立即触发。