Paul R D, Padmanabhan R, Lopez D M
Cancer Res. 1984 Oct;44(10):4480-6.
Spleen cells from BALB/c mice bearing a syngeneic mammary adenocarcinoma nonspecifically destroy xenogeneic targets following in vitro induction with mammary tumor-associated antigens. Studies were undertaken to characterize the effector cell population(s) mediating this "innocent bystander" cytotoxicity reaction. Fractionation experiments using phagocyte-depleted spleen cells revealed that the effector population was adherent to nylon wool columns. Flow cytometric analysis of the nylon-adherent cells revealed the presence of a minor population of Thy 1.2+ cells. Following treatment of the nylon-adherent cells with anti-Thy 1.2 and complement, the cytotoxic activity was abolished. Furthermore, when those cells expressing the Thy 1.2 antigen were positively selected by cell sorting, they were able to mediate the cytotoxic reaction. In contrast, nylon-adherent Thy 1.2-negative cells were unable to mediate the reaction following selection by cell sorting. Depletion studies with anti-Lyt 1 or anti-Lyt 2 and complement also abolished this cytotoxic response. Additional studies demonstrated that nylon-adherent spleen cells from mammary tumor-bearing mice were not able to lyse natural killer cell-sensitive targets. These data suggest that the cells which effect tumor antigen-induced "innocent bystander" cytotoxicity, or their activated precursors, are nylon-adherent Thy 1.2+, Lyt 1+2+ T-cells.
携带同基因乳腺腺癌的BALB/c小鼠的脾细胞在体外经乳腺肿瘤相关抗原诱导后,可非特异性地破坏异种靶细胞。开展了研究以鉴定介导这种“无辜旁观者”细胞毒性反应的效应细胞群体。使用去除吞噬细胞的脾细胞进行的分级分离实验表明,效应细胞群体可黏附于尼龙毛柱。对尼龙黏附细胞进行的流式细胞术分析显示存在少量Thy 1.2+细胞。用抗Thy 1.2和补体处理尼龙黏附细胞后,细胞毒性活性消失。此外,当通过细胞分选对表达Thy 1.2抗原的细胞进行阳性选择时,它们能够介导细胞毒性反应。相比之下,尼龙黏附的Thy 1.2阴性细胞在通过细胞分选选择后无法介导该反应。用抗Lyt 1或抗Lyt 2和补体进行的去除研究也消除了这种细胞毒性反应。进一步的研究表明,来自携带乳腺肿瘤小鼠的尼龙黏附脾细胞无法裂解自然杀伤细胞敏感的靶细胞。这些数据表明,介导肿瘤抗原诱导的“无辜旁观者”细胞毒性的细胞或其活化前体是尼龙黏附的Thy 1.2+、Lyt 1+2+ T细胞。