AUTOIMMUNE T-LYMPHOCYTE CELL LINES IN DIABETES

这项拨款申请的长期目标是研究 胰腺β细胞破坏的过程，这是一个主要的 人类和实验性糖尿病的特征。 的 BioBreeding/Worcester（BB/Wor）中的自发性糖尿病综合征 大鼠是一种独特的胰岛素依赖型糖尿病模型， 研究细胞介导的自身免疫性破坏， β细胞 有待检验的假设是， 糖尿病是β细胞特异性的，部份地介导的 淋巴样细胞的效应群，其渗透并破坏 胰腺β细胞 为了解决这个问题。实验 提出了利用一种新的、已建立的胰岛移植 浸润的单核细胞相互作用的系统 胰岛β细胞可以在治疗过程中进行检查。 隔离病变。 具体而言，以下研究目标将 （1）。 浸润胰腺的淋巴细胞 胰岛移植物可以在体外维持和克隆？ 2.）的情况。让T细胞 来源于浸润淋巴细胞的细胞系在体内响应于 抗原刺激？ 3.）第三章 从胰岛移植物中提取T细胞 代表一个同质的群体，他们的功能是确定的 MHC类或II类限制性模式？ 做T细胞系 表达细胞毒性功能？ 4.） T细胞爪是否拥有 体内致糖尿病潜力？ 这一具体目标的重点是 评估T细胞系诱导疾病的可能作用， 以及导致疾病过程的细胞事件。 阐明自身免疫性疾病的发病机制 胰腺β细胞的破坏在临床上是重要的， β细胞是人类和哺乳动物的主要病理部位， 实验性糖尿病 所使用的方法主要是免疫学性质的 包括：组织培养，单克隆抗体，混合 淋巴细胞和细胞毒性测定，过继转移， 免疫组织化学、流式细胞术、组织学和时相， 光镜

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.