INITIATOR T CELLS IN DELAYED-TYPE HYPERSENSITIVITY

迟发性超敏反应(DTH)是活体反应的例子 T细胞介导的免疫。先前的研究表明，24小时 迟发型超敏反应是由于抗原/MHC-II类限制性的CD4+(L3T4+)T细胞所致。 这些DTH效应T细胞被称为“炎症性”(Th-1)。 因为T细胞的特征是在体外产生 I12、干扰素-γ和淋巴毒素。然而，较新的工作来自 我们的实验室已经表示，潜伏期是由于顺序 两种不同T细胞的作用。早期起作用的T细胞产生 通过致敏启动迟发型变态反应的抗原特异性T细胞因子 释放5-羟色胺的组织。在苦味酸氯(PCL)接触中 敏感度、PCL-F为原型因子。5-羟色胺介导的 PCL-F诱导的血管活性允许晚期患者的局部招募 作用，迟发型变态反应-炎症T细胞。这项提案将重点放在 介导迟发型变态反应的T细胞亚群。我们假设 以下是：1)启动DTH的T细胞正在发挥作用， 原始的，相对胸腺无关的T细胞；2)DTH- 启动T细胞具有“三阴性”表面表型： Thy1+、Ly1+、Ly2-、L3T4-、CD3-或CD3-lo；以及3)DTH启动T 细胞只有抗原受体，不受MHC限制。如果 这些假设是正确的，那么系统性转移性潜伏期将 被证明是由于CD4-DTH的协同作用- 启动和CD4+DTH-炎性T细胞。 因此，我们计划将这种相对胸腺无关的特性 T细胞及其抗原特异性产物。我们计划隔离和 通过选择这些细胞独特的表面表型来克隆它们 通过我们的能力诱导这种启动DTH的T细胞 体外培养。我们将继续尝试提纯PCL-F并希望 最终克隆编码这种潜伏期启动的基因 因此，它可以与传统的T细胞受体进行比较。 我们和其他人的研究表明，启动DTH的T 细胞参与接触和迟发性超敏反应， 对肿瘤、胃肠道炎症和 自身免疫力。因此，我们对细胞和分子的研究 迟发型超敏反应启动的各个方面具有广泛的免疫学相关性。

Delayed type hypersensitivity (DTH) reactions are in vivo examples of T cell mediated immunity. Previous work indicated that 24 hr DTH was due to antigen/MHC-Class II-restricted CD4+ (L3T4+)T cells. These DTH effector T cells have been called "inflammatory" (Th-1) T cells because they are characterized by in vitro production of I12, interferon-gamma and lymphotoxin. However, newer work from our laboratory has indicated that DTH is due to the sequential action of two different T cells. An early-acting T cell produces antigen-specific T cell factor that initiates DTH by sensitizing tissues for serotonin release. In picryl chloride (PCl) contact sensitivity, PCl-F is the prototype factor. The serotonin-mediated vasoactivity induced by PCl -F allows local recruitment of the late acting, DTH-inflammatory T cells. This proposal will focus on the T cell subpopulations that mediate DTH. We hypothesize the following: 1) that DTH-initiating T cells are functioning, primitive, relatively thymic-independent T cells; 2) that DTH- initiating T cells have a "triple-negative" surface phenotype of: Thy1+,Ly1+,Ly2-,L3T4-,CD3-or CD3-lo; and 3) that DTH-initiating T cells have antigen-only receptors that are non-MHC-restricted. If these hypotheses are correct, then systemic transferred DTH will be shown to be due to the synergistic action of CD4- DTH- initiating, and CD4+ DTH-inflammatory T cells. Thus, we plan to characterize this relatively thymic-independent T cell and its antigen-specific product. We plan to isolate and clone these cells by selecting for their unique surface phenotype and through our ability to induce this DTH-initiating T cell in vitro. We will continue to attempting to purify PCl-F and hope eventually to clone the genes that encode for this DTH-initiating factor so that it can be compared to conventional T cell receptors. Our studies, and those of others, indicate that DTH-initiating T cells are involved in contact and delayed hypersensitivity, resistance to tumors, gastrointestinal inflammation, and autoimmunity. Thus our studies on the cellular and molecular aspects of DTH initiation have broad immunological relevance.