Fujiwara H, Kinouchi T, Tsuchida T, Aoki H, Hamaoka T
Gan. 1982 Oct;73(5):766-72.
The present study investigates the role of helper T cells in preventing tolerance in effector T cells responsible for syngeneic tumor immunity. Tolerance in T cell-mediated immune responses against X5563 plasmacytoma was induced in syngeneic C3H/He mice by intravenous (iv) administration of 7,000 R X-irradiated X5563 tumor cells. Since the anti-X5563 tumor tolerance was observed irrespective of whether the tumor cells had been modified with trinitrophenyl (TNP) hapten prior to iv inoculation, the ability of TNP-reactive helper T cells to prevent the tolerance induced by iv inoculation of TNP-X5563 tumor cells was examined. TNP-reactive helper T cell activity was generated in C3H/He mice by immunization with TNP-isologous mouse gamma-globulin after inoculation with the TNP-conjugate of a non-immunogenic co-polymer of D-glutamic acid and D-lysine. Intravenous inoculation with TNP-modified X5563 cells induced tolerance in mice not primed with TNP. However, such tolerance was prevented in mice in which TNP-reactive helper T cell activity had been generated. These results indicate that helper T cells play a crucial role in preventing effector T cell tolerance. The mechanisms by which tolerance induction in effector T cells is circumvented are discussed in relation to the generation and delivery of signals required for T cell activation.
本研究调查辅助性T细胞在防止负责同基因肿瘤免疫的效应T细胞产生耐受性方面的作用。通过静脉注射7000拉德X射线照射的X5563肿瘤细胞，在同基因C3H/He小鼠中诱导针对X5563浆细胞瘤的T细胞介导免疫反应的耐受性。由于无论肿瘤细胞在静脉接种前是否用三硝基苯（TNP）半抗原进行了修饰，均观察到抗X5563肿瘤耐受性，因此检测了TNP反应性辅助性T细胞防止静脉接种TNP-X5563肿瘤细胞诱导的耐受性的能力。在用D-谷氨酸和D-赖氨酸的非免疫原性共聚物的TNP缀合物接种后，通过用TNP-同种异体小鼠γ球蛋白免疫，在C3H/He小鼠中产生TNP反应性辅助性T细胞活性。静脉接种TNP修饰的X5563细胞在未用TNP致敏的小鼠中诱导耐受性。然而，在已产生TNP反应性辅助性T细胞活性的小鼠中，这种耐受性得到了防止。这些结果表明辅助性T细胞在防止效应T细胞耐受性方面起着关键作用。结合T细胞活化所需信号的产生和传递，讨论了规避效应T细胞耐受性诱导的机制。
