Yamasaki T, Yamashita J, Handa H, Namba Y, Hanaoka M
No To Shinkei. 1982 Nov;34(11):1067-75.
The effects of adult thymectomy in C 57 BL/6 mice on in vivo and in vitro responses to syngeneic methylcholanthrene-induced glioma (203-glioma) were investigated in order to analyse the role of T cell subpopulation in relation to the antitumor immunity. The tumor growth in adult mice thymectomized 3 weeks before subcutaneous inoculation of tumor cells was significantly suppressed. On the other hand, in mice thymectomized 7 or 10 weeks before tumor cell inoculation, the tumor growth was enhanced resulting in shorter mean survival time. The cytotoxic activity of the regional lymph node T cells in the former mice was increased from the beginning after tumor cell inoculation with peak observed on day 14 and maintained for about 4 weeks, while it was extremely decreased in the latter mice. The marked enhancement of cytotoxic activity in the former mice is probably due to a reduced proportion of short-lived T lymphocyte population after adult thymectomy. In contrast, the low level of cytotoxic activity in the latter mice may be due to a gradual reduction of long-lived T lymphocyte population in addition to short-lived T lymphocyte population after adult thymectomy. The cytotoxic activity was specific for 203-glioma cells and almost completely eliminated with anti-Thy-1 monoclonal antibody and complement. The surface markers of these killer T cells were checked with the results that in normal mice Lyt-1-.2.3+ and Lyt-1+.2.3+ cells participate in cytotoxic reaction. In mice thymectomized 3-10 weeks before tumor cell inoculation, however, Lyt-1+.2.3+ killer T cells were not detected suggesting strongly that the progenitors of Lyt-1+.2.3+ killer T cells are short-lived cells in contrast to those of Lyt-1-.2.3+ killer T cells which survive more than 10 weeks after adult thymectomy. The tumor growth was also significantly suppressed by the intravenous adoptive transfer of sensitized lymphocytes obtained from mice thymectomized 3 weeks before tumor cell inoculation. This effect of tumor suppression was disappeared by the pretreatment of infused lymphocytes with anti-Thy-1 monoclonal antibody and complement. These evidences may suggest that in tumor bearing mice short-lived suppressor T cells or their precursors exist and regulate the growth and differentiation of killer T cells and that adult thymectomy affects immunoregulation, possibly by altering the generation of suppressor T cells.
为分析T细胞亚群在抗肿瘤免疫中的作用,研究了成年C57BL/6小鼠胸腺切除对同基因甲基胆蒽诱导的胶质瘤(203 - 胶质瘤)体内和体外反应的影响。在皮下接种肿瘤细胞前3周进行胸腺切除的成年小鼠中,肿瘤生长受到显著抑制。另一方面,在肿瘤细胞接种前7或10周进行胸腺切除的小鼠中,肿瘤生长加快,导致平均存活时间缩短。前一组小鼠区域淋巴结T细胞的细胞毒活性在肿瘤细胞接种后从一开始就增加,在第14天达到峰值并维持约4周,而后一组小鼠中该活性则极度降低。前一组小鼠细胞毒活性的显著增强可能是由于成年胸腺切除后短命T淋巴细胞群体比例降低所致。相反,后一组小鼠细胞毒活性水平较低可能是由于成年胸腺切除后除短命T淋巴细胞群体外,长寿T淋巴细胞群体也逐渐减少。细胞毒活性对203 - 胶质瘤细胞具有特异性,并且几乎完全被抗Thy - 1单克隆抗体和补体消除。检查了这些杀伤性T细胞的表面标志物,结果显示在正常小鼠中Lyt - 1-.2.3+和Lyt - 1+.2.3+细胞参与细胞毒反应。然而,在肿瘤细胞接种前3 - 10周进行胸腺切除的小鼠中,未检测到Lyt - 1+.2.3+杀伤性T细胞,这强烈提示与Lyt - 1-.2.3+杀伤性T细胞不同,Lyt - 1+.2.3+杀伤性T细胞的祖细胞是短命细胞,后者在成年胸腺切除后存活超过10周。从肿瘤细胞接种前3周进行胸腺切除的小鼠中获得的致敏淋巴细胞经静脉内过继转移也显著抑制了肿瘤生长。用抗Thy - 1单克隆抗体和补体对输注的淋巴细胞进行预处理后,这种肿瘤抑制作用消失。这些证据可能表明,在荷瘤小鼠中存在短命抑制性T细胞或其前体,它们调节杀伤性T细胞的生长和分化,并且成年胸腺切除可能通过改变抑制性T细胞的产生来影响免疫调节。