Nakayama E, Shiku H, Takahashi T, Oettgen H F, Old L J
Proc Natl Acad Sci U S A. 1979 Jul;76(7):3486-90. doi: 10.1073/pnas.76.7.3486.
BALB/c x-ray-induced leukemia RL male 1 is strongly immunogenic for (BALB/c x C57BL/6)F1 mice. Transplants of RL male 1 regressed after initial growth, and after tumor regression mice could resist repeated inocula of 10(7) RL male 1 cells. Spleen cells from immunized mice after in vitro stimulation with RL male 1 were cytotoxic for RL male 1 cells in 3-hr 51Cr assays. Pretreatment of immune spleen cells with Thy-1, Lyt-2, or Lyt-3 antisera and complement eliminated cytotoxic activity, indicating that effector cells for RL male 1 lysis are T cells. Tests with other target cells showed little or no cytotoxicity. Analysis of the specificity of T-cell killing of RL male 1 by competitive inhibition assays with unlabeled cells indicated that only RL male 1 could inhibit killing; other BALB/c tumors (13 x-ray or murine leukemia virus-induced leukemias and three myelomas) failed to inhibit lysis of RL male 1. A range of alloantisera and heteroantisera were tested for their capacity to block lytic activity in the absence of added complement. H-2d antisera and Lyt-2 and -3 antisera blocked lysis, the latter at the level of the effector cell. Antisera to other cell surface alloantigens, murine leukemia virus-related antigens, and immunoglobulins did not block RL male 1 lysis. Thus, T cells from mice immunized against RL male 1 recognize an individually distinct or unique antigen that does not appear to be related to any of the serologically defined cell surface determinants of RL male 1. In its restriction to a single leukemia, the RL male 1 antigen resembles the individually distinct antigens of chemically induced tumors and other tumor types of rodents.
BALB/c 经 X 射线诱导的白血病 RL 雄性 1 对(BALB/c×C57BL/6)F1 小鼠具有强烈的免疫原性。RL 雄性 1 的移植瘤在初始生长后会消退,并且在肿瘤消退后,小鼠能够抵抗 10⁷ 个 RL 雄性 1 细胞的重复接种。用 RL 雄性 1 体外刺激免疫小鼠后的脾细胞,在 3 小时的⁵¹Cr 测定中对 RL 雄性 1 细胞具有细胞毒性。用 Thy-1、Lyt-2 或 Lyt-3 抗血清及补体预处理免疫脾细胞可消除细胞毒性活性,表明裂解 RL 雄性 1 的效应细胞是 T 细胞。对其他靶细胞的测试显示几乎没有细胞毒性。通过用未标记细胞进行竞争性抑制试验分析 RL 雄性 1 的 T 细胞杀伤特异性,结果表明只有 RL 雄性 1 能够抑制杀伤;其他 BALB/c 肿瘤(13 种经 X 射线或鼠白血病病毒诱导的白血病及 3 种骨髓瘤)均不能抑制 RL 雄性 1 的裂解。测试了一系列同种异体抗血清和异种抗血清在不添加补体的情况下阻断裂解活性的能力。H-2d 抗血清以及 Lyt-2 和 -3 抗血清可阻断裂解,后者在效应细胞水平发挥作用。针对其他细胞表面同种异体抗原、鼠白血病病毒相关抗原和免疫球蛋白的抗血清均不能阻断 RL 雄性 1 的裂解。因此,用 RL 雄性 1 免疫的小鼠的 T 细胞识别一种个体独特的抗原,该抗原似乎与 RL 雄性 1 的任何血清学定义的细胞表面决定簇均无关。在对单一白血病的限制性方面,RL 雄性 1 抗原类似于化学诱导肿瘤和啮齿动物其他肿瘤类型的个体独特抗原。