Selvan R S, Nagarkatti P S, Nagarkatti M
Department of Biology, Virginia Polytechnic Institute, State University, Blacksburg.
Int J Cell Cloning. 1991 Nov;9(6):594-605. doi: 10.1002/stem.5530090609.
1,3-Bis(chloroethyl)-1-nitrosourea (BCNU) has been shown to "cure" over 90% of the mice bearing the syngeneic tumor LSA, and the cured mice acquire elevated levels of tumor-specific immunity. In the present study, we report for the first time the establishment and characterization of several tumor-specific CD8+ cytotoxic T cell (CTL) clones from splenic T cells of BCNU-cured LSA mice. Many of these clones were found to be strongly cytotoxic to LSA but not to a different H-2b tumor target such as EL-4, or the natural killer (NK)-susceptible target YAC-1, NK-resistant target P815, or con A or LPS blasts from H-2b mice. Some of the clones showed a moderate level of cytotoxicity to the NK-susceptible target YAC-1. The relative roles of interleukins such as IL-2, IL-4 or IL-6 in supporting the proliferative response of some LSA-activated CTL clones were analyzed. As expected, recombinant human (rh) IL-2 alone supported the proliferative response of activated CTL clones. Addition of recombinant murine (rm) IL-4 or rhIL-6 alone to the culture failed to influence the response. Also, in combination with rhIL-2, neither rmIL-4 nor rhIL-6 appreciably augmented rhIL-2-supported proliferative response of CTL clones. These studies may provide insights for the development of effective approaches to modulate function and activity of effector T cells.
1,3-双（氯乙基）-1-亚硝基脲（BCNU）已被证明能“治愈”90%以上携带同基因肿瘤LSA的小鼠，且治愈的小鼠获得了更高水平的肿瘤特异性免疫力。在本研究中，我们首次报告了从BCNU治愈的LSA小鼠脾脏T细胞中建立并鉴定了几个肿瘤特异性CD8 + 细胞毒性T细胞（CTL）克隆。发现这些克隆中的许多对LSA具有强烈的细胞毒性，但对不同的H-2b肿瘤靶标如EL-4，或自然杀伤（NK）敏感靶标YAC-1、NK抗性靶标P815，或来自H-2b小鼠的刀豆蛋白A或脂多糖刺激的细胞没有细胞毒性。一些克隆对NK敏感靶标YAC-1表现出中等水平的细胞毒性。分析了白细胞介素如IL-2、IL-4或IL-6在支持一些LSA激活的CTL克隆增殖反应中的相对作用。正如预期的那样，单独的重组人（rh）IL-2支持激活的CTL克隆的增殖反应。单独向培养物中添加重组鼠（rm）IL-4或rhIL-6未能影响反应。此外，与rhIL-2联合使用时，rmIL-4和rhIL-6均未明显增强rhIL-2支持的CTL克隆增殖反应。这些研究可能为开发调节效应T细胞功能和活性的有效方法提供见解。
