LeFor A T, Eisenthal A, Rosenberg S A
Surgery Branch, National Cancer Institute, Bethesda, MD 20892.
J Immunol. 1988 Jun 1;140(11):4062-9.
Murine splenocytes incubated for 3 to 4 days with the lymphokine, IL-2, acquire the ability to mediate the lysis of a wide variety of fresh tumor targets in short term chromium release assays. We undertook these studies to examine the lysis of splenocyte blasts by these lymphokine-activated killer (LAK) cells, to help gain an understanding of the mechanisms of target cell recognition. Allogeneic blast targets but not syngeneic blasts are highly lysable by LAK effector cells. By using congenic mice, we have shown that only the H-2 haplotype, and not other differences, determines the recognition and lysis of a blast target cell. Both Con A- and LPS-induced allogeneic splenocyte blasts are lysed and thus lectin-induced binding of effectors and targets is unlikely to be responsible for this effect. By using in vivo antibody depletion experiments, we showed that different populations of effector cells mediate the lysis of tumor cells and allogeneic blasts. Furthermore, we observed that the lysis of a susceptible blast can be inhibited only by like cold blasts of the same haplotype. These results suggest that there is a separate population of LAK cells responsible for the lysis of each type of blast target cell. Though syngeneic blasts were not lysed by LAK cells, TNP modification of syngeneic blasts converted them into cells that were recognized and lysed by LAK cells. In cold target inhibition studies, the lysis of fresh syngeneic tumor was not inhibited by TNP-modified syngeneic blasts. Similarly, the lysis of TNP-modified syngeneic blasts was not inhibited by fresh tumor. By using in vitro antibody depletion, we determined that TNP-modified blasts are lysed by LAK cells with Thy-1+ precursors, in distinction to the Thy-1- precursors involved in tumor cell lysis. Elimination of the Thy-1+ cells at the precursor stage completely abrogated the lysis of blasts but did not diminish the lysis of tumor cells. We conclude that IL-2 promotes the growth of numerous populations of effector cells with Thy-1+ precursors that have a narrow range of specificity, in contrast to the broad lytic ability for fresh tumor mediated by LAK cells with Thy-1- precursors.
将小鼠脾细胞与淋巴因子白细胞介素-2一起培养3至4天，在短期铬释放试验中，这些脾细胞获得了介导多种新鲜肿瘤靶细胞裂解的能力。我们进行了这些研究，以检测这些淋巴因子激活的杀伤细胞（LAK细胞）对脾细胞母细胞的裂解作用，从而有助于了解靶细胞识别机制。LAK效应细胞可高效裂解异基因母细胞靶细胞，但不能裂解同基因母细胞。通过使用同源小鼠，我们发现只有H-2单倍型而非其他差异决定了对母细胞靶细胞的识别和裂解。刀豆蛋白A和脂多糖诱导的异基因脾细胞母细胞均被裂解，因此效应细胞与靶细胞的凝集素诱导结合不太可能是造成这种效应的原因。通过体内抗体清除实验，我们表明不同群体的效应细胞介导肿瘤细胞和异基因母细胞的裂解。此外，我们观察到，只有相同单倍型的同基因冷母细胞才能抑制易感母细胞的裂解。这些结果表明，存在一个单独的LAK细胞群体负责每种类型母细胞靶细胞的裂解。虽然LAK细胞不能裂解同基因母细胞，但对同基因母细胞进行三硝基苯（TNP）修饰可将其转化为能被LAK细胞识别和裂解的细胞。在冷靶抑制研究中，TNP修饰的同基因母细胞不能抑制新鲜同基因肿瘤的裂解。同样，新鲜肿瘤也不能抑制TNP修饰的同基因母细胞的裂解。通过体外抗体清除实验，我们确定TNP修饰的母细胞被具有Thy-1+前体的LAK细胞裂解，这与参与肿瘤细胞裂解的Thy-1-前体不同。在前体阶段消除Thy-1+细胞可完全消除母细胞的裂解，但不会减少肿瘤细胞的裂解。我们得出结论，与具有Thy-1-前体的LAK细胞介导的对新鲜肿瘤的广泛裂解能力相比，白细胞介素-2促进了众多具有Thy-1+前体且特异性范围较窄的效应细胞群体生长。
