Fujiwara H, Fukuzawa M, Yoshioka T, Nakajima H, Hamaoka T
J Immunol. 1984 Sep;133(3):1671-6.
The present study determines the Ly phenotype of T cells mediating tumor cell rejection in vivo and investigates some of cellular mechanisms involved in the in vivo protective immunity. C3H/HeN mice were immunized to syngeneic X5563 plasmacytoma by intradermal (i.d.) inoculation of viable X5563 tumor cells, followed by the surgical resection of the tumor. Spleen cells from these immune mice were fractionated by treatment with anti-Lyt antibodies plus complement, and each Lyt subpopulation was tested for the reconstituting potential of in vivo protective immunity in syngeneic T cell-depleted mice (B cell mice). When C3H/HeN B cell mice were adoptively transferred with Lyt-1-2+ T cells from the above tumor-immunized mice, these B cell mice exhibited an appreciable cytotoxic T lymphocyte (CTL) response to the X5563 tumor, whereas they failed to resist the i.d. challenge of X5563 tumor cells. In contrast, the adoptive transfer of Lyt-1+2- anti-X5563 immune T cells into B cell mice produced complete protection against the subsequent tumor cell challenge. Although no CTL or antibody response against X5563 tumors was detected in the above tumor-resistant B cell mice, these mice were able to retain Lyt-1+2- T cell-mediated delayed-type hypersensitivity (DTH) responses to the X5563 tumor. These results indicate that Lyt-1+2- T cells depleted of the Lyt-2+ T cell subpopulation containing CTL or CTL precursors are effective in in vivo protective immunity, and that these Lyt-1+2- T cells implement their in vivo anti-tumor activity without inducing CTL or antibody responses. The mechanism(s) by which Lyt-1+2- T cells function in vivo for the implementation of tumor-specific immunity is discussed in the context of DTH responses to the tumor-associated antigens and its related Lyt-1+2- T cell-mediated lymphokine production.
本研究确定了在体内介导肿瘤细胞排斥的T细胞的Ly表型,并研究了体内保护性免疫所涉及的一些细胞机制。通过皮内(i.d.)接种活的X5563肿瘤细胞,使C3H/HeN小鼠对同基因的X5563浆细胞瘤产生免疫,随后进行肿瘤的手术切除。用抗Lyt抗体加补体处理这些免疫小鼠的脾细胞,对每个Lyt亚群进行测试,以检测其在同基因T细胞耗竭小鼠(B细胞小鼠)中重建体内保护性免疫的潜力。当将上述肿瘤免疫小鼠的Lyt-1-2+ T细胞过继转移到C3H/HeN B细胞小鼠时,这些B细胞小鼠对X5563肿瘤表现出明显的细胞毒性T淋巴细胞(CTL)反应,然而它们未能抵抗X5563肿瘤细胞的皮内攻击。相反,将Lyt-1+2-抗X5563免疫T细胞过继转移到B细胞小鼠中,可对随后的肿瘤细胞攻击产生完全保护。尽管在上述抗肿瘤B细胞小鼠中未检测到针对X5563肿瘤的CTL或抗体反应,但这些小鼠能够保留Lyt-1+2- T细胞介导的对X5563肿瘤的迟发型超敏反应(DTH)。这些结果表明,不含CTL或CTL前体的Lyt-2+ T细胞亚群的Lyt-1+2- T细胞在体内保护性免疫中有效,并且这些Lyt-1+2- T细胞在不诱导CTL或抗体反应的情况下发挥其体内抗肿瘤活性。在对肿瘤相关抗原的DTH反应及其相关的Lyt-1+2- T细胞介导的淋巴因子产生的背景下,讨论了Lyt-1+2- T细胞在体内发挥肿瘤特异性免疫作用的机制。