MOLECULAR BASIS FOR T LYMPHOCYTE FACTOR ACTIVITY

T 淋巴细胞因子活性的分子基础

• 批准号: 3127649
• 负责人: FRANK W. FITCH
• 金额: $ 13.53万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-05-01 至 1990-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3127649
• 关键词: T lymphocyte; apolipoproteins; cell growth regulation; clone cells; genetic manipulation; genetic recombination; helper T lymphocyte; high performance liquid chromatography; immunochemistry; immunoregulation; interleukin 2; leukocyte activation /transformation; lymphokines; macrophage; monoclonal antibody

T lymphocytes play an integral role in both cellular and humoral immune responses, carrying out direct effector functions such as cytolysis as well as mediating regulatory functions via secreted lymphokines. T cell activation antigen can be defined only in operational terms: development of functional activity, lymphokine production, or proliferation. The antigen receptor accounts for the specificity of T cell responses. Antigenic stimulation induces lymphokine secretion, including interleukin 2 (IL-2), and also causes an increase in the number of cell surface receptors for IL-2 which, in turn, augments the proliferative response produced by IL-2. The biochemical events which follow stimulation of T cells have not been fully characterized. T cell responses are modulated in a variety of ways. IL-2 has a profound immunoregulatory effect on the cell which produces it: When cells which secrete IL-2 are exposed to IL-2, they become unresponsive to antigen. Gamma interferon acts on macrophages to increase expression of class II major histocompatibility antigens which are required for effective antigen presentation. Resting macrophages secrete apoprotein E which has profound inhibitory immunoregulatory activity; this secretion is reduced when macrophages are stimulated. Thus, there are several feedback pathways that can influence T cell responses. We intend to characterize the cellular and biochemical processes which are associated with activation of T lymphocytes. In particular, we want to distinguish between those events that are initiated by stimulation with antigen and those that are induced by lymphokines such as IL-2. We also intend to characterize the processes involved in the negative regulation of T cell responses. In particular, we want to determine the basis for unresponsiveness to antigen which is induced when cloned murine T cells are exposed to IL-2. We also want to determine the role of apoprotein-E, produced by macrophages, in the regulation of the response of T cells. In these studies, we will use cloned T cells, fixed antigen-presenting cells, monoclonal antibodies, and lymphokines produced by recombinant DNA technology. Thus, discriminating model systems are available for studying the metabolic events induced by specific stimuli.

T淋巴细胞在细胞免疫和体液免疫中起着不可或缺的作用， 反应，进行直接效应功能，如细胞溶解以及 通过分泌的淋巴因子介导调节功能。 T细胞 激活抗原只能用操作术语来定义： 功能活动、淋巴因子产生或增殖。 的 抗原受体解释了T细胞应答的特异性。 抗原刺激诱导淋巴因子分泌，包括白细胞介素2 （IL-2），也导致细胞表面受体数量增加， 而IL-2反过来又增强了由 IL-2。 刺激T细胞后发生的生化事件并没有 被充分定性。 T细胞反应在多种免疫调节中被调节。 的方式 IL-2对细胞具有深刻的免疫调节作用， 产生它：当分泌IL-2的细胞暴露于IL-2时，它们 对抗原无反应。 γ干扰素作用于巨噬细胞， 增加II类主要组织相容性抗原表达， 是有效抗原呈递所必需的。 静息巨噬细胞分泌 载脂蛋白E具有深刻的抑制免疫调节活性;这 当巨噬细胞受到刺激时，分泌减少。 由此可见，有 几个反馈途径，可以影响T细胞的反应。 我们打算 来表征与之相关的细胞和生物化学过程， 激活T淋巴细胞。 特别是，我们想区分 在由抗原刺激引发的那些事件之间， 这些是由淋巴因子如IL-2诱导的。 我们还打算 表征参与T细胞负调节的过程 应答 特别是，我们希望确定 当克隆的鼠T细胞被诱导时， 暴露于IL-2。 我们还想确定载脂蛋白E的作用， 由巨噬细胞产生，调节T细胞的反应。 在 在这些研究中，我们将使用克隆的T细胞，固定的抗原呈递细胞， 单克隆抗体和由重组DNA产生的淋巴因子 技术. 因此，判别模型系统是可供研究的 由特定刺激引起的代谢事件。