Analysis of mediators which regulate T-T cell interactions involved in regulatory immune responses.

本研究通过利用不同的T细胞克隆来研究：(1)T细胞成熟环境对辅助性T(Th)细胞、增强型(Ta)细胞和抑制性T(Ts)细胞的影响，这些细胞被证明构建了一个最小的调节电路来调节II类限制性Th细胞的辅助功能，以及(2)T细胞参与抑制MHC限制性Th细胞激活的机制。本研究证明了以下几点：(1)T细胞成熟环境中的I-A分子主要影响锁孔斑点血蓝蛋白特异的Th细胞库，而Ta库由I-A和I-E两个分子共同决定。这些曲目不受抗原预置的影响。产生ts细胞因子的ts细胞系不受T细胞成熟环境的影响，而是由抗原前…的I-J单倍型决定。更多的nting细胞(APC)被用于抗原的启动。相反，新型同源型TS细胞以限制性方式抑制II类限制性Th细胞的功能，受到T细胞成熟环境的I-A和I-E分子的影响。这些结果证明了T细胞库的产生有两种不同的机制：外源抗原启动前T细胞成熟环境的II类分子的选择和APC和抗原联合启动的选择。(2)活化的CD_4~+T细胞可抑制ANN冲击的APC诱导的Th克隆胞内钙离子浓度的升高。(3)TS克隆抑制Th1和Th2克隆的细胞内钙反应具有较强的选择性，而其他的CD4和CD3克隆则不能抑制Th1和Th2克隆的Ca2+反应。CD8克隆可通过释放IL10和TNFalphabeta抑制Th细胞的增殖反应和辅助功能。相反，CD4tS克隆只抑制Th细胞介导的抗体的形成，其因素不同于任何已知的白介素类，包括γ&gt；Fn和转化生长因子β&gt；。因此，CD_4~+和CD_8~+T细胞克隆通过不同的机制介导对免疫应答的抑制作用。较少

The present studies were carded out by utilizing various T cell clones to characterize : (1) The influence of the T cell maturation environment on a repertoire of helper T (Th) cells, T augmenting (Ta) cells, and suppressor T (Ts) cells, which were shown to construct a minimal regulatory circuit to regulate a helper function of class II-restricted Th cells, and (2) the mechanisms of involved in suppressive T cell regulation of MHC-restricted Th cell activation of B cells. The present studies demonstrated the several important points.(1) A repertoire of keyhole limpet hemocyanin-specific Th cells was influenced predominantly by I-A molecule of the T cell maturation environment, whereas a repertoire of Ta was determined by both I-A and I-E molecules. These repertoires were not influenced by the priming with antigen. A repertoire of Ts cell factor-producing Ts cells was not influenced by the T cell maturation environment, but rather was determined by the I-J haplotype of the antigen-prese … More nting cells (APC) utilized for priming with antigen. In contrast, a repertoire of novel cognate type Ts cells, which inhibit class II-restricted Th cell function in a restriction-restricted manner, was influenced by both I-A and I-E molecules of the T cell maturation environment. These results demonstrate the two distinct mechanisms for generating a T cell repertoire : a selection by class II molecules of the T cell maturation environment before the priming with foreign antigen and a selection by priming with APC and antigen.(2) The activated CD4^+ Ts cells could inhibit the increase of intracellular Ca2^+ of Th Clones induced by anngen-pulsed APC. The identity of MHC restriction-specificities was required for the instant suppression of Ca2^+ influx of Th clones, while a longer period of activation of Ts clones was needed to suppress the response of Th clones having different MHC restrictions.(3) A strict selectivity was found in the suppressive activity of Ts clones in that Ts clones could suppress the Ca2^+ responses of Th1 and Th2 clones but not other CD4^+ Ts clones.(4) Both CD4^+ and CD8^+ Ts clones released soluble immunosuppressive factors upon stimulation with immobiized anti-CD3 antibody. CD8^+ clones could suppress the proliferative response and helper function of Th cells by releasing IL10 and TNFalphabeta, respectively. In contrast, CD4^+ Ts clones suppress only Th cell-mediated antibody formation by the factors different from any known interleukins including _<gamma>FN and TGF_<beta>. Therefore, CD4^+ and CD8^+ Ts clones mediate suppressive effect on immune responses by the different mechaisms. Less