MOLECULAR BASIS FOR T LYMPHOCYTE FACTOR ACTIVITY

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。

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.