AUTOIMMUNE T-LYMPHOCYTE CELL LINES IN DIABETES

糖尿病中的自身免疫 T 淋巴细胞系

• 批准号: 3241122
• 负责人: BRUCE A WODA
• 金额: $ 14.46万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-01-01 至 1992-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3241122
• 关键词: T lymphocyte; autoimmune disorder; cell mediated lymphocytolysis test; clone cells; cytolysis; diabetes mellitus; flow cytometry; gene expression; histology; immunochemistry; laboratory mouse; laboratory rat; leukocyte activation /transformation; major histocompatibility complex; membrane proteins; mixed lymphocyte reaction test; monoclonal antibody; pancreatic islet transplantation; pancreatic islets; prediabetic state; tissue /cell culture

The long range goal of this grant application is to study the process of pancreatic beta cell destruction which is a primary characteristic of both human and experimental diabetes. The spontaneous diabetic syndrome in the BioBreeding/Worcester (BB/Wor) rat presents an unique model of insulin-dependent diabetes in which to study the cell-mediated autoimmune destruction targeted to the beta cell. The hypothesis to be tested is that the autoimmune lesion of diabetes is beta-cell specific and. in part. mediated by an effector population of lymphoid cells which infiltrate and destroy pancreatic beta cells. To address this problem. experiments are proposed which utilize a novel, established islet transplantation system whereby the interaction of infiltrating mononuclear cells and islet beta cells can be examined during the course of the insulates lesion. Specifically, the following research aims will be addressed: 1.) can the lymphocytes which infiltrate pancreatic islet grafts be maintained and cloned in vitro? 2.) do the T cell lines derived from infiltrating lymphocytes respond in vivo to antigenic stimulation? 3.) do T cell lines from islet grafts represent a homogeneous population and is their function determined by MHC class or class II restriction patterns? do T cell lines express a cytotoxic function? 4.) do the T cell Tines possess a diabetogenic potential in vivo? The focus of this specific aim is to evaluate a possible role for the T cell lines to induce disease and the cellular events leading to the disease process. The elucidation of the mechanisms involved in the autoimmune destruction of pancreatic beta cells is important clinically since the beta cell is the primary site of pathology in both human and experimental diabetes. The methodologies to be used are primarily immunologic in nature and include: tissue culture, monoclonal antibodies, mixed lymphocyte and cytotoxicity assays, adoptive transfer, immunohistochemistry, flow cytometry, histology, and phase and light microscopy.

这项拨款申请的长远目标是研究 胰腺β细胞破坏的过程是一种原发的 人类糖尿病和实验性糖尿病的特点。这个 生物育种中的自发性糖尿病综合征(BB/WOR) 大鼠呈现一种独特的胰岛素依赖型糖尿病模型 研究靶向细胞介导的自身免疫破坏 β细胞。 需要检验的假设是，自体免疫损伤 糖尿病是β细胞特异性的，而且。在一定程度上。由An调解 渗入和破坏的淋巴样细胞的效应群 胰岛β细胞。来解决这个问题。实验是 提出了一种新的、成熟的胰岛移植 浸润性单个核细胞相互作用的系统 和胰岛β细胞可以在过程中检查 隔离损伤。具体地说，以下研究目标将 地址：1.)浸润性胰腺的淋巴细胞能否 胰岛移植物能否在体外维持和克隆？)T细胞 来自浸润性淋巴细胞的细胞系在体内对 抗原刺激？3)从胰岛移植来的T细胞系 代表同类总体，其功能是否已确定 通过MHC类或II类限制模式？T细胞系 表达细胞毒功能？4.)T细胞Tines是否具有 体内发生糖尿病的潜力？这一具体目标的重点是 评估T细胞系在诱发疾病中的可能作用 以及导致疾病过程的细胞事件。 自身免疫相关机制的阐明 破坏胰岛β细胞在临床上很重要，因为 β细胞是人类和人类的主要病理部位 实验性糖尿病。 将使用的方法主要是免疫学性质的。 包括：组织培养、单抗、混合 淋巴细胞和细胞毒性检测，过继转移， 免疫组织化学、流式细胞术、组织学和时相分析 光学显微镜。