INITIATOR T CELLS IN DELAYED-TYPE HYPERSENSITIVITY

迟发型超敏反应中的启动 T 细胞

• 批准号: 3140567
• 负责人: PHILIP William ASKENASE
• 金额: $ 16.5万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3140567
• 关键词: CD3 molecule; CD4 molecule; T cell receptor; T lymphocyte; antibody formation; autoimmune disorder; cellular immunity; cellular pathology; cytokine; delayed hypersensitivity; helper T lymphocyte; immunogenetics; inflammation; inflammatory bowel diseases; interferons; laboratory mouse; lymphokines; major histocompatibility complex; molecular cloning; picrotoxin; serotonin; surface antigens; tumor necrosis factor beta

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.

迟发型超敏反应（DTH）是体内的例子 T细胞介导的免疫。 以前的工作表明，24小时 DTH是由于抗原/MHC II类限制性CD 4+（L3 T4+）T细胞。 这些DTH效应T细胞被称为“炎性”（Th-1） T细胞，因为它们的特征是在体外产生 I12，干扰素-γ和α-光氧合酶。 然而，来自 我们的实验室已经表明，DTH是由于连续的 两种不同的T细胞。 一个早期作用的T细胞产生 一种抗原特异性T细胞因子，通过致敏引发DTH 释放血清素。 苦基氯（PCl）接触 灵敏度，PCl-F是原型因子。 胡萝卜素介导的 由PCl-F诱导的血管活性允许晚期的局部募集。 DTH-炎性T细胞。 本提案将侧重于 介导DTH的T细胞亚群。 我们假设 以下：1）DTH起始T细胞发挥功能， 原始的，相对胸腺独立的T细胞; 2）DTH- 起始T细胞具有以下“三阴性”表面表型： Thy 1+、Ly 1+、Ly 2-、L3 T4-、CD 3-或CD 3-lo;和3）DTH起始T 细胞具有非MHC限制性的仅抗原受体。 如果 这些假设是正确的，那么全身转移性DTH将 被证明是由于协同作用的CD 4- DTH- 启动和CD 4 + DTH-炎性T细胞。 因此，我们计划描述这种相对胸腺独立的 T细胞及其抗原特异性产物。 我们计划隔离和 通过选择它们独特的表面表型来克隆这些细胞 通过我们诱导DTH起始T细胞的能力， 体外 我们将继续尝试提纯PCl-F， 最终克隆编码DTH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，DTH启动T 细胞参与接触和迟发型超敏反应， 抗肿瘤、胃肠道炎症， 自身免疫 因此，我们对细胞和分子的研究 DTH起始的方面具有广泛的免疫学相关性。