CELL SURFACE STRUCTURES IN T LYMPHOCYTE ACTIVATION

T淋巴细胞在细胞和体液中起着中心作用 免疫反应，执行直接效应功能，如 细胞溶解以及通过分泌的 淋巴因子。而TCR则说明了T细胞的特异性 反应，其他T细胞表面分子也影响T细胞 回应。一些T细胞表面结构与T细胞的类别相关 限制其反应的MHC抗原：CD8+“细胞溶解”T细胞 受I类MHC抗原限制，而CD4+辅助性T细胞 受第II类MHC抗原限制。CD4+T细胞已经被细分 进一步基于分泌型淋巴因子阵列：T(H)1细胞 T(H)2细胞分泌IL-2和干扰素-γ，但不分泌IL-4或IL-5 IL-4和IL-5，而不是IL-2或干扰素-γ。这一区别也是 与这些子集之间的功能差异相关：T(H)L调用 T(H)2细胞有效介导迟发型超敏反应 “帮助”B细胞的反应。这些CD4+T细胞亚群也会对 与免疫调节过程不同：干扰素-γ抑制 T(H)2克隆增殖，而T(H)L克隆不增殖。T(H)1细胞 经IL-2预处理的患者在随后通过 IL-2可促进T(H)2细胞的增殖。 高浓度抗TcR单抗处理T(H)L克隆 抑制IL-2诱导的增殖；这种治疗增强了 T(H)2克隆的增殖。信号通路也不同； 刺激TCR可引起心肌细胞内钙离子浓度升高 T(H)L，但在T(H)2克隆中不存在。这项研究的总体目标是 提案是进一步描述一些监管过程的特征，这些过程 差别化调控小鼠CD4+T细胞亚群功能。 有四个具体目标：1)确定生物化学基础 小鼠T(H)1和T(H)2信号转导的差异 克隆；2)确定选择性刺激的基础 脾贴壁细胞(AC)和T(H)_2对T(H)L细胞的增殖作用 B细胞；3)确定其他可能的选择性影响， 促进T(H)1、T(H)2等小鼠T细胞的活化和扩增 4)研制能区分小鼠T(H)L的单抗 和T(H)2个T个呼叫子集。拟议的研究应提供见解 进入控制T细胞生长和功能的调控过程。

T lymphocytes play a central role in cellular and humoral immune responses, carrying out direct effector functions such as cytolysis as well as mediating regulatory functions via secreted lymphokines. While the TCR accounts for the specificity of T cell responses, other T cell surface molecules also influence T cell responses. Some T cell surface structures correlate with the class of MHC antigen which restricts their responses: CD8+ "cytolytic" T cells are restricted by class I MHC antigens while CD4+ 'helper' T cells are restricted by class II MHC antigens. CD4+ T cells have been subdivided further on the basis of the array of secreted lymphokines: T(H)1 cells secrete IL-2 and IFN-gamma but not IL-4 or IL-5 while T(H)2 cells secrete IL-4 and IL-5 but not IL-2 or IFN-gamma. This distinction also correlates with functional differences between these subsets: T(H)l calls mediate delayed-type hypersensitivity while T(H)2 cells efficiently 'help' B cells responses. These CD4+ T cell subsets also respond differently to immunoregulatory processes: IFN-gamma inhibits the proliferation of T(H)2 clones, but not of T(H)l clones. T(H)1 cells pretreated with IL-2 do not respond when stimulated subsequently through the TCR; proliferation of T(H)2 cells is enhanced by IL-2 pre--treatment. Treatment of T(H)l clones with high concentrations of anti-TCR mAb inhibits IL-2-induced proliferation; this treatment augments proliferation of T(H)2 clones. Signalling pathways also differ; stimulation of the TCR induces an increase in intracellular (Ca2+) in T(H)l but not in T(H)2 clones. The general goal of this research proposal is to characterize further some of the regulatory processes that control differentially the functions of murine CD4+ T lymphocyte subsets. There are four Specific Aims: 1) To determine the biochemical basis for the differences in signal transduction observed in murine T(H)1 and T(H)2 clones; 2) To determine the basis for the selective stimulation of proliferation of T(H)l cells by splenic adherent cells (AC) and of T(H)2 cells by B cells; 3) To identify other possible selective influences that favor activation and expansion of T(H)1, T(H)2, and other murine T cell subsets; and 4) To develop mAb which can distinguish between murine T(H)l and T(H)2 T call subsets. The proposed studies should provide insights into the regulatory processes that control T cell growth and function.