MOLECULAR BASIS FOR T LYMPHOCYTE FACTOR ACTIVITY

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。 因此， 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。

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.