Tomita S, Fujiwara H, Yamane Y, Sano S, Nakajima H, Izumi Y, Arai H, Kawanishi Y, Tsuchida T, Hamaoka T
Jpn J Cancer Res. 1986 Feb;77(2):182-9.
The present study demonstrates the intratumoral infiltration of lymphocytes mediating anti-tumor delayed-type-hypersensitivity (DTH) responses as well as in vivo protective immunity. The surface phenotype and tumor specificity of these effector lymphocytes were determined. X5563 tumor-infiltrating lymphoid cells were obtained from the tumor mass of syngeneic C3H/HeN mice 2 weeks after the intradermal inoculation of 10(6) viable X5563 tumor cells. These lymphoid cells consisted of Thy-1-positive (29-35%), surface immunoglobulin-positive (16-29%), large granule-positive (15-25%) and esterase-staining-positive (10-20%) cells. They were tested for anti-X5563 DTH responses by utilizing a local adoptive transfer system and for tumor-neutralizing activity in a Winn assay. The results indicate that X5563 tumor-infiltrating lymphoid cells exhibited appreciable anti-X5563 DTH responses and conveyed complete protection against the tumor. Treatment of these lymphoid cells with anti-Thy-1.2 or anti-Lyt antibodies plus complement revealed that the in vivo anti-tumor immune responses were mediated predominantly by a Lyt-1+2- T cell subset. Such Lyt-1+2- T cell-mediated immunity was tumor-specific, since X5563-infiltrating and syngeneic MH134 hepatoma-infiltrating cells exhibited DTH response and tumor-neutralizing activity selectively against the respective tumor cell types. Thus, these results indicate that tumor-specific in vivo-protective Lyt-1+2- T cells infiltrate into the tumor mass. The results are discussed in the context of 1) the interrelation of DTH responses and the tumor protection mediated by the Lyt-1+2- T cell subset and 2) possible cellular interactions between Lyt-1+2- T cells and co-existing nonspecific tumoricidal effector cells such as macrophages.
本研究证明了介导抗肿瘤迟发型超敏反应(DTH)以及体内保护性免疫的淋巴细胞在肿瘤内浸润。确定了这些效应淋巴细胞的表面表型和肿瘤特异性。在皮内接种10(6)个活的X5563肿瘤细胞2周后,从同基因C3H/HeN小鼠的肿瘤块中获取X5563肿瘤浸润淋巴细胞。这些淋巴细胞由Thy-1阳性(29-35%)、表面免疫球蛋白阳性(16-29%)、大颗粒阳性(15-25%)和酯酶染色阳性(10-20%)的细胞组成。通过利用局部过继转移系统检测它们对X5563的DTH反应,并在Winn试验中检测其肿瘤中和活性。结果表明,X5563肿瘤浸润淋巴细胞表现出明显的抗X5563 DTH反应,并对肿瘤提供完全保护。用抗Thy-1.2或抗Lyt抗体加补体处理这些淋巴细胞表明,体内抗肿瘤免疫反应主要由Lyt-1+2-T细胞亚群介导。这种Lyt-1+2-T细胞介导的免疫是肿瘤特异性的,因为X5563浸润细胞和同基因MH134肝癌浸润细胞分别对各自的肿瘤细胞类型表现出DTH反应和肿瘤中和活性。因此,这些结果表明肿瘤特异性的体内保护性Lyt-1+2-T细胞浸润到肿瘤块中。在1)DTH反应与Lyt-1+2-T细胞亚群介导的肿瘤保护之间的相互关系以及2)Lyt-1+2-T细胞与共存的非特异性杀肿瘤效应细胞(如巨噬细胞)之间可能的细胞相互作用的背景下讨论了这些结果。