MOLECULAR BASIS FOR T LYMPHOCYTE FACTOR ACTIVITY

T 淋巴细胞因子活性的分子基础

• 批准号: 3127652
• 负责人: FRANK W. FITCH
• 金额: $ 10.2万
• 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/3127652
• 关键词: T lymphocyte; antibody dependent killer cell; apolipoproteins; cell growth regulation; clone cells; genetic manipulation; genetic recombination; helper T lymphocyte; high performance liquid chromatography; immunochemistry; immunoregulation; interleukin 2; laboratory mouse; laboratory rat; leukocyte activation /transformation; lymphokines; macrophage; monoclonal antibody; nucleic acid probes

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都发挥着不可或缺的作用 应答，也执行直接效应功能，如细胞溶解 通过分泌淋巴因子发挥调节功能。T细胞 激活抗原只能在操作术语中定义：开发 功能活动、淋巴因子的产生或增殖。这个 抗原受体解释了T细胞反应的特异性。 抗原刺激诱导包括白介素2在内的淋巴因子的分泌 (IL-2)，并导致细胞表面受体数量增加。 对于IL-2来说，它反过来又增强了由 IL-2。刺激T细胞后发生的生化事件并没有 已经被完全定性了。T细胞的反应是以多种方式调节的 方式。IL-2对细胞有深刻的免疫调节作用， 产生它：当分泌IL-2的细胞暴露在IL-2中时，它们 对抗原没有反应。伽马干扰素作用于巨噬细胞以 增加II类主要组织相容性抗原的表达，这些抗原是 有效的抗原呈递所必需的。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，分泌会减少。因此，有以下几种 可以影响T细胞反应的几种反馈途径。我们打算 来描述与之相关的细胞和生化过程 T淋巴细胞被激活。特别是，我们想要区分 在那些由抗原刺激引发的事件和 这些细胞是由IL-2等淋巴因子诱导的。我们还打算 描述参与T细胞负调控的过程 回应。特别是，我们希望确定以下基础 当克隆的小鼠T细胞被克隆时，对抗原诱导的无应答 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，在调节T细胞的反应。在……里面 这些研究，我们将使用克隆的T细胞，固定的抗原提呈细胞， 重组DNA产生的单抗和淋巴因子 技术因此，判别模型系统可用于研究 由特定刺激引起的代谢事件。