CELL SURFACE STRUCTURES IN T LYMPHOCYTE ACTIVATION

T淋巴细胞在细胞和体液免疫中发挥核心作用 免疫反应，执行直接效应子功能，如 细胞溶解以及通过分泌介导调节功能 淋巴因子 而TCR解释了T细胞的特异性， 其他T细胞表面分子也影响T细胞的免疫应答。 应答 一些T细胞表面结构与T细胞的类型相关。 限制其反应的MHC抗原：CD 8+“溶细胞”T细胞是 受I类MHC抗原的限制，而CD 4+“辅助”T细胞是 受II类MHC抗原限制。 CD 4 + T细胞已被细分 进一步基于分泌的淋巴因子：T（H）1细胞的阵列， 分泌IL-2和IFN-γ，但不分泌IL-4或IL-5，而T（H）2细胞分泌 IL-4和IL-5，而不是IL-2或IFN-γ。 这种区别也 与这些子集之间的功能差异相关：T（H）1调用 介导迟发型超敏反应，而T（H）2细胞有效地介导迟发型超敏反应， “帮助”B细胞反应。 这些CD 4 + T细胞亚群也对 与免疫调节过程不同：IFN-γ抑制 T（H）2克隆增殖，而T（H）1克隆不增殖。 T（H）1细胞 用IL-2预处理后，当随后通过 IL-2预处理可促进T（H）_2细胞的增殖。 用高浓度的抗TCR mAb处理T（H）1克隆 抑制IL-2诱导的增殖;这种治疗增强 T（H）2克隆的增殖。 信号通路也不同; TCR的刺激诱导细胞内（Ca 2+）的增加， T（H）1的克隆，而T（H）2的克隆则不存在。 本研究的总体目标是 建议进一步描述一些监管过程， 差异化调控小鼠CD 4 + T淋巴细胞亚群功能。 有四个具体目的：1）确定生物化学基础， 在小鼠T（H）1和T（H）2中观察到的信号转导差异 克隆; 2）确定选择性刺激的基础 脾贴壁细胞（AC）对T（H）1细胞的增殖和T（H）2细胞的增殖 通过B细胞; 3）鉴定其他可能的选择性影响， 有利于T（H）1、T（H）2和其它鼠T细胞的活化和扩增 4）开发能够区分小鼠T（H）1亚群的mAb， 和T（H）2 T调用子集。 拟议的研究应提供见解 进入控制T细胞生长和功能的调节过程。

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.