Fujiwara H, Moriyama Y, Suda T, Tsuchida T, Shearer G M, Hamaoka T
J Immunol. 1984 Mar;132(3):1571-7.
The present study was designed to investigate the generation of trinitrophenyl (TNP)-reactive helper T cell activity potent enough to induce the regression of a syngeneic tumor; this occurs by augmenting antitumor-specific immunity through T-T cell interaction. Mice whose skin was painted with trinitrochlorobenzene (TNCB) exhibited a variety of anti-TNP T cell responses, including delayed-type hypersensitivity (DTH) and cytotoxic T cell responses, as well as helper T cell activity. Pretreatment of C3H/He mice with TNP-conjugated copolymer of D-glutamic acid and lysine (TNP-D-GL) or cyclophosphamide, which have been shown, respectively, to inactivate TNP-specific suppressor T cells or suppressor T cells in general, exhibited a slight or marginal augmentation of DTH and cytotoxic potentials when tested 5 wk after TNCB painting. In contrast, the same pretreatment regimens induced an appreciably amplified generation of anti-TNP helper T cell activity. This amplified TNP-helper T cell activity was demonstrated to enhance cytotoxic responses to antigens other than TNP in an antigen-nonspecific way. In fact, such helper T cells enhanced antitumor CTL responses when co-cultured with spleen cells from syngeneic X5563 plasmacytoma-bearing mice in the presence of TNBS-modified X5563 tumor cells. This amplified TNP-helper cell system was utilized for its immunotherapeutic potential. When TNCB was injected into X5563 tumor mass of syngeneic C3H/He mice in which the amplified TNP-helper T cell activity had been generated, an appreciable number of growing tumors was observed to regress. This contrasted with the low incidence of tumor regression observed in mice in which TNP-helper activity had been induced by TNCB painting without inactivation of suppressors. Thus, the present model provides an effective immunotherapeutic manipulation for eliciting enhanced in vivo tumor regression, and emphasizes a role of helper T cells in augmentation of syngeneic tumor immunity.
本研究旨在探讨三硝基苯基（TNP）反应性辅助性T细胞活性的产生，这种活性足以诱导同基因肿瘤的消退；这是通过T细胞与T细胞相互作用增强抗肿瘤特异性免疫来实现的。用三硝基氯苯（TNCB）涂抹皮肤的小鼠表现出多种抗TNP T细胞反应，包括迟发型超敏反应（DTH）和细胞毒性T细胞反应，以及辅助性T细胞活性。分别用已证明可使TNP特异性抑制性T细胞失活或一般抑制性T细胞失活的TNP偶联的D-谷氨酸和赖氨酸共聚物（TNP-D-GL）或环磷酰胺对C3H/He小鼠进行预处理，在TNCB涂抹后5周进行检测时，DTH和细胞毒性潜能略有或边缘性增强。相比之下，相同的预处理方案诱导了明显增强的抗TNP辅助性T细胞活性的产生。这种增强的TNP辅助性T细胞活性被证明以抗原非特异性方式增强对TNP以外抗原的细胞毒性反应。事实上，当在TNBS修饰的X5563肿瘤细胞存在的情况下，与来自同基因X5563浆细胞瘤荷瘤小鼠的脾细胞共培养时，这种辅助性T细胞增强了抗肿瘤CTL反应。这种增强的TNP辅助细胞系统因其免疫治疗潜力而被利用。当将TNCB注射到已产生增强的TNP辅助性T细胞活性的同基因C3H/He小鼠的X5563肿瘤块中时，观察到相当数量的生长肿瘤出现消退。这与在未使抑制性细胞失活的情况下通过TNCB涂抹诱导TNP辅助活性的小鼠中观察到的低肿瘤消退发生率形成对比。因此，本模型提供了一种有效的免疫治疗操作，用于引发体内增强的肿瘤消退，并强调了辅助性T细胞在增强同基因肿瘤免疫中的作用。
