EFFECT OF IFN-ALPHA AND IL-2 ON IN-VIVO GENERATION OF KILLER CELLS

IFN-α和IL-2对体内杀伤细胞生成的影响

• 批准号: 3811184
• 负责人: R PURI
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3811184
• 关键词: cytotoxic T lymphocyte; immunotherapy; interferons; interleukin 2; killer cells; laboratory mouse; leukocyte activation /transformation; leukocyte antigen typing; liver cells; natural killer cells; neoplasm /cancer immunotherapy; passive immunization; spleen

In this project, we have studied in-vivo generation of LAK, NK, and CTL activities in response to IL-2 and IFN-alpha administration in the organs of mice. The data indicate that administration of IL-2 for 3 consecutive days is capable of generating LAK activity and enhance NK mediated cytotoxicity from splenic and hepatic lymphocytes. Administration of a mixture of IFN-alpha and IL-2 enhanced LAK activity compared to group treated with IL- alone. In both spleen and liver cells, LAK activity was enhanced. The induction of NK activity was also observed by IFN-alpha and IL-2 administration but the results were variable. Continued administration of IFN-alpha and IL-2 for 7 days caused synergistic augmentation of LAK activity in both liver and spleen cells. IL-2 administration alone caused generation of LAK but activity was lower than observed after 3 days of therapy. These studies indicate that potent LAK or 'super LAK' cells are generated by IL-2 and IFN-alpha-therapy in vivo and this may explain, at least in part, the synergistic anti-tumor effects of this combination therapy in mouse as well as in man. We have also analysed the phenotype of proliferating cells in the spleens and livers of mice from various treatmen groups. IL-2 administration caused an increase in the percentage Thy 1.2 an Asialo-GM-1 positive cells in both organs. The administration of both IL-2 and IFN-alpha also increased Thy 1.2 and Asialo-GM-1 positive cells and thi increase in the liver appeared to be greater than caused by IL-2 alone. The CTL response is currently being investigated.

本课题研究了LAK、NK和CTL的体内诱导 器官中响应IL-2和IFN-α给药的活性 的 小鼠数据表明连续3天施用IL-2 能够产生LAK活性并增强NK介导的细胞毒性 脾和肝淋巴细胞中提取。施用以下物质的混合物： IFN-α和IL-2增强LAK活性 一个人脾细胞和肝细胞LAK活性增强。的 IFN-α和IL-2也可诱导NK细胞活性 但结果是可变的。继续给药 IFN-α和IL-2联合作用7天可协同增强LAK细胞活性 在肝和脾细胞中的活性。IL-2单独给药引起 产生LAK，但活性低于3天后观察到的 疗法这些研究表明，有效的LAK或“超级LAK”细胞是 产生的IL-2和IFN-α-治疗在体内，这可以解释，在 至少部分地，该组合的协同抗肿瘤作用 在小鼠和人的治疗中，我们还分析了 不同处理小鼠脾和肝中增殖细胞 组IL-2给药引起Thy 1.2和Thy 1.4百分比的增加， 两个器官中的去唾液酸GM-1阳性细胞。IL-2的施用 IFN-α也增加Thy 1.2和Asialo-GM-1阳性细胞， 肝脏中的增加似乎大于单独由IL-2引起的。的 目前正在研究CTL应答。