Smyth M J, Kershaw M H, Darcy P K, Trapani J A
Cellular Cytotoxicity Laboratory, The Austin Research Institute, Heidelberg, Victoria, Australia.
Xenotransplantation. 1998 May;5(2):146-53. doi: 10.1111/j.1399-3089.1998.tb00020.x.
The popliteal lymph node cells of immunocompetent mice generated a strong in vitro cytotoxic response to footpad injection of several human tumor cell lines and the resulting mouse effector cells predominantly used a perforin-mediated cytotoxic mechanism. A relatively minor FasL-dependent cytotoxic response to CEM-CCRF and Jurkat leukemias, but not colon carcinoma COLO 205 cells, was also detected in immunized perforin-deficient mice. In vitro depletion of CD3+ CD8+ T cells, but not CD4+ T or NK1.1+ cells, completely inhibited lysis of human tumor cells, suggesting that CD3+ CD8+ T cells were effectors of perforin-mediated xenospecific cytotoxicity. Xenospecific cytotoxic T cells from wild-type mice were extremely efficient at rejecting tumor when adoptively transferred into scid mice bearing established COLO 205, CEM-CCRF, or Jurkat tumor xenografts. By contrast, cytotoxic T lymphocytes of perforin-deficient mice had no effect on the growth of established tumor xenografts. These data indicate that perforin, and hence direct cytotoxicity, plays a key role in the ability of adoptively transferred CD8+ cytotoxic T lymphocytes to eradicate established xenografts.
免疫活性小鼠的腘淋巴结细胞对足垫注射多种人类肿瘤细胞系产生了强烈的体外细胞毒性反应，并且由此产生的小鼠效应细胞主要采用穿孔素介导的细胞毒性机制。在免疫的穿孔素缺陷小鼠中，也检测到对CEM-CCRF和Jurkat白血病细胞（但对结肠癌COLO 205细胞没有）相对较弱的FasL依赖性细胞毒性反应。体外去除CD3 + CD8 + T细胞而非CD4 + T细胞或NK1.1 +细胞，完全抑制了对人类肿瘤细胞的裂解，这表明CD3 + CD8 + T细胞是穿孔素介导的异种特异性细胞毒性的效应细胞。当野生型小鼠的异种特异性细胞毒性T细胞被过继转移到携带已建立的COLO 205、CEM-CCRF或Jurkat肿瘤异种移植物的scid小鼠中时，它们在排斥肿瘤方面极其有效。相比之下，穿孔素缺陷小鼠的细胞毒性T淋巴细胞对已建立的肿瘤异种移植物的生长没有影响。这些数据表明，穿孔素以及直接细胞毒性，在过继转移的CD8 +细胞毒性T淋巴细胞根除已建立的异种移植物的能力中起关键作用。
