Rahman S M, Kawashima K, Nakashima I, Nagase F
Department of Immunology, Nagoya University School of Medicine, Japan.
Cancer Res. 1988 Nov 15;48(22):6450-4.
T-cell clone K4L, the cell surface phenotypes of which were Thy-1+, Lyt-1-, Lyt-2+, and L3T4-, was established from the spleen cells of a murine leukemia L1210-immune mouse. Clone K4L was specific for antigen B on L1210, and this antigen was different from antigen A for which the previously reported T-cell clone K7L was specific. K4L possessed cytotoxicity and tumor growth-inhibitory activity against both L1210 and antigen A loss variant, L1210-K7L-, but not against syngeneic tumor P388 or L5178Y. Previously we showed that antigen A was lost frequently for generation of antigen loss variants. In contrast, antigen B was barely found to be lost. When mice were inoculated with L1210 plus a moderate dose of K4L, the tumor grew after initial suppression but this newly emerging tumor was K4L sensitive and was ultimately rejected. The mice initially given L1210 plus K4L attained a high-grade tumor-specific immunity for rejecting the subsequently challenged high-dose (10(7) cells) L1210. This immunity did not involve any bystander antitumor activity against the third party P388 lymphoma that was injected together with L1210 but accompanied the increase in the L1210-specific cytotoxic T-lymphocyte activity. Evidence was provided that the live L1210, the outgrowth of which was inhibited by K4L, induced an effective immune response of radiation-sensitive host lymphocytes including L3T4+ helper T-cells. Taken together, our results show a novel strategy for inducing high-grade host-dependent antitumor immunity by use of a cytotoxic T-lymphocyte clone specific for a stable tumor-specific transplantation antigen.
T细胞克隆K4L是从一只患鼠白血病L1210免疫小鼠的脾细胞中建立的，其细胞表面表型为Thy-1+、Lyt-1-、Lyt-2+和L3T4-。克隆K4L对L1210上的抗原B具有特异性，且该抗原与先前报道的T细胞克隆K7L所特异性识别的抗原A不同。K4L对L1210和抗原A缺失变异体L1210-K7L-均具有细胞毒性和肿瘤生长抑制活性，但对同基因肿瘤P388或L5178Y则无此活性。先前我们表明，抗原A在抗原缺失变异体的产生过程中经常丢失。相比之下，几乎未发现抗原B丢失。当给小鼠接种L1210加中等剂量的K4L时，肿瘤在最初受到抑制后仍会生长，但新出现的肿瘤对K4L敏感并最终被排斥。最初接种L1210加K4L的小鼠获得了高级别的肿瘤特异性免疫力，可排斥随后受到攻击的高剂量（10⁷个细胞）L1210。这种免疫力不涉及对与L1210一起注射的第三方P388淋巴瘤的任何旁观者抗肿瘤活性，而是伴随着L1210特异性细胞毒性T淋巴细胞活性的增加。有证据表明，其生长受到K4L抑制的活L1210可诱导包括L3T4+辅助性T细胞在内的辐射敏感宿主淋巴细胞产生有效的免疫反应。综上所述，我们的结果显示了一种通过使用对稳定的肿瘤特异性移植抗原有特异性的细胞毒性T淋巴细胞克隆来诱导高级别的宿主依赖性抗肿瘤免疫力的新策略。
