VISUALIZING INSULITIS--IDDM PATHOGENESIS AND THERAPY

描述：（改编自研究者摘要）：胰岛素依赖性 糖尿病（IDDM）是一种严重衰弱的自身免疫性疾病， 通过自身免疫过程选择性破坏胰岛β细胞， 包括淋巴细胞浸润非肥胖糖尿病（NOD）小鼠 自发地发展为胰岛素依赖型糖尿病，并显示出人类糖尿病的许多特征。 胰岛素依赖型糖尿病。已经证明，疾病的效应期是 在过继性转移研究中，需要CD4+和 CD8+ T细胞用于最大的疾病转移。为了研究β细胞的损失和 胰岛炎前的分子和细胞事件，使用 将开发生物发光报告，评估空间和时间 淋巴细胞运输和β细胞丢失的特征。我们将雇用一名 成像战略，以便分析收养儿童的贩运情况， 转移细胞，以了解更多关于IDDM的病理生理学， 由过继转移的细胞介导的免疫治疗的位点。使用 通过这些成像策略，我们可以评估初始抗原接触的时间， 在体内，并定位这种相互作用的网站，并确定是否树突状细胞 细胞局部或局部淋巴结内被自身抗原脉冲刺激。的研究 胰腺β细胞质量的真实的时间将允许深入分析 胰岛β细胞破坏的时间事件。研究概述 本项目拟探讨过继转移CD4+的可行性 T细胞，被转导以表达“调节”蛋白，作为过继性T细胞的一种形式。 自身免疫性疾病的细胞介导的免疫疗法。如果这些研究表明 过继性T细胞介导的基因治疗，通过递送“调节”蛋白 自身免疫性炎症的部位，它提供了一个有吸引力的可能性， 包括胰岛素依赖型糖尿病在内的自身免疫性疾病的人类基因治疗。的兴奋 这些研究涉及基因治疗对 炎症性病变，直接观察这种现象，并准备 这种形式的治疗对人类疾病的适应性。积极的结果提高 将这项技术从NOD小鼠模型转移到 人类疾病

DESCRIPTION: (Adapted from the Investigator's abstract): Insulin-dependent diabetes mellitus (IDDM) is a severely debilitating autoimmune disease caused by selective destruction of the islet beta cells by an autoimmune process that involves lymphocyte infiltration. The non-obese diabetic (NOD) mouse spontaneously develops IDDM and shows many of the characteristics of human IDDM. It has been demonstrated that the effector phase of the disease is mediated by T cells, and, in adoptive transfer studies, requires both CD4+ and CD8+ T cells for maximal disease transfer. To study beta cell loss and the molecular and cellular events that precede insulitis, noninvasive assays using bioluminescent reporters will be developed that assess the spatial and temporal features of lymphocyte trafficking and beta cell loss. We will employ an imaging strategy that allows an analysis of the trafficking of adoptively transferred cells to learn more about pathophysiology of IDDM and to localize the site of immunotherapy mediated by the adoptively transferred cells. Using these imaging strategies we can assess the timing of initial antigen encounter in vivo, and localize the sites of this interaction and determine if dendritic cells get pulsed with autoantigen locally or in regional nodes. The study in real time of pancreatic beta cell mass will allow an in depth analysis of the temporal events surrounding islet beta cell destruction. The studies outlined in this project intend to explore the feasibility of adoptive transfer of CD4+ T cells, transduced to express "regulatory" proteins as a form of adoptive T cell mediated immunotherapy of autoimmune disease. If these studies demonstrate adoptive T cell mediated gene therapy, by delivering the "regulatory" proteins to sites of autoimmune inflammation, it offers an attractive possibility for human gene therapy of autoimmune diseases including IDDM. The excitement of these studies relates to the specific targeting of gene therapy to the inflammatory lesion, the direct observation of this phenomenon, and the ready adaptability of this form of therapy to human disease. Positive results raise the possibility of transferring this technology from the NOD mouse model to human disease.