Lymphokine-activated killer cells: lysis of fresh syngeneic natural killer-resistant murine tumor cells by lymphocytes cultured in interleukin 2.
Lymphokine-activated killer cells: lysis of fresh syngeneic natural killer-resistant murine tumor cells by lymphocytes cultured in interleukin 2.
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淋巴细胞因子激活的杀伤细胞：用在白细胞介素 2 中培养的淋巴细胞裂解新鲜的同源自然杀伤剂耐药小鼠肿瘤细胞。
作者：
M. Rosenstein;I. Yron;Y. Kaufmann;S. Rosenberg
在淋巴因子、白细胞介素 2 (IL-2) 中培养短短 2 天的正常脾细胞在 4 小时 51Cr 释放测定中对新鲜同基因自然杀伤耐药肿瘤细胞以及自然杀伤敏感 YAC 细胞产生裂解活性。淋巴因子激活杀伤 (LAK) 细胞不会裂解同源新鲜淋巴细胞，但会裂解同源伴刀豆球蛋白 A 诱导的淋巴细胞母细胞。裂解不是由于凝集素或异种血清的存在而引起的，并且似乎是在 IL-2 中激活的淋巴细胞的固有特性。这种激活似乎是普遍的，因为以这种方式激活的所有小鼠品系的淋巴细胞对新鲜肿瘤靶细胞都表现出相似的裂解模式。为了表征导致这种裂解的细胞，我们使用单克隆抗体和补体通过耗尽技术分析了这些细胞上表面标记的表型表达。这些研究表明 LAK 细胞的前体是 Thy-1+，并且不粘附于塑料或尼龙毛。当用抗Thy-1.2或抗Lyt-2.2单克隆抗体和补体处理LAK细胞时，同系肿瘤的裂解受到抑制，但用抗Lyt-1.2单克隆抗体和补体处理则不然，表明观察到的裂解活性是由于Thy-1+ Lyt-1-2+细胞所致。此外，在细胞毒性测定中添加抗 Lyt-2 或 LFA-1 单克隆抗体可以抑制 LAK 细胞介导的裂解。冷靶抑制分析表明，同源肿瘤细胞通过识别正常淋巴细胞或淋巴细胞母细胞上不存在的决定簇而被裂解。在 IL-2 中生长的淋巴细胞对新鲜实体瘤细胞的裂解可能在肿瘤-宿主免疫相互作用的研究中有价值。 IL-2 激活细胞裂解肿瘤的生物学意义需要进一步研究。
Normal splenocytes that are cultured in the lymphokine, interleukin 2 (IL-2), for as short as 2 days develop lytic activity for fresh syngeneic natural killer-resistant tumor cells as well as natural killer-sensitive YAC cells in a 4-hr 51Cr release assay. Lymphokine-activated killer (LAK) cells do not lyse syngeneic fresh lymphocytes but do lyse syngeneic concanavalin A-induced lymphocyte blasts. Lysis is not due to the presence of lectin or xenogeneic serum and appears to be an intrinsic property of lymphocytes activated in IL-2. The activation appears universal in that lymphocytes from all strains of mice activated in this manner exhibited similar patterns of lysis for fresh tumor target cells. To characterize the cells responsible for this lysis, we analyzed the phenotypic expression of surface markers on these cells with depletion techniques using monoclonal antibody and complement. These studies indicate that the precursor of the LAK cell is Thy-1+ and nonadherent to plastic or nylon wool. Lysis of syngeneic tumor was inhibited when LAK cells were treated with an anti-Thy-1.2, or anti-Lyt-2.2 monoclonal antibody and complement but not with anti-Lyt-1.2 monoclonal antibody and complement, indicating that the observed lytic activity was due to a Thy-1+ Lyt-1-2+ cell. Furthermore, LAK cell-mediated lysis could be inhibited by the addition of anti-Lyt-2 or LFA-1 monoclonal antibody to cytotoxicity assays. Cold target inhibition analysis revealed that the syngeneic tumor cells were lysed by recognition of a determinant not present on normal lymphocytes or lymphocyte blasts. This lysis of fresh solid tumor cells by lymphoid cells grown in IL-2 may be of value in the study of tumor-host immunological interactions. The biological significance of tumor lysis by IL-2-activated cells requires further study.