PATHOGENESIS AND PREVENTION OF AUTOIMMUNE DIABETES

目前的申请是为一个新的计划项目赠款的资金 自身免疫性糖尿病的发病机制和预防。 的 这项资金的目的是让四名调查人员谁曾工作 在过去一起，在未来继续做。 程序 由三个核心支持的四个项目组成。 这些项目是 项目1：C.A.珍妮薇，PI。 该项目重点关注CD 8 T 可以将急性糖尿病转移到NOD小鼠的细胞。 这些CD 8克隆 T细胞系在三小时内进入胰岛， 老鼠测试 我们将研究它们的归巢，构建TCR转基因 小鼠，并识别他们检测到的β细胞抗原。 项目2：R.A. Flavell，PI. 本项目旨在分析模型中的公差 使用正常和NOD转基因小鼠，询问是否存在 NOD小鼠的广义缺陷耐受性，并确定其 机制 项目3：交流嗨，派。 该项目将研究 自身抗原谷氨酸脱羧酶（GAD）在 NOD小鼠。 我们已经观察到强烈的促进insultis和一些 糖尿病在这些小鼠中的增加。 该项目的目的是研究 这种加速，使用对GAD特异的TCR转基因。 项目四： RS.Sherwin，PI. 该项目主要集中在 胰岛素特异性保护性T细胞克隆的表征。 他们的 作用机制及其发展的特点将使用 TCR转基因技术，有望研制出疫苗。 这四个项目 由三个核心设施支持：核心A，行政核心， C. Janeway PI;核心B，动物核心，FS。 Wong，PI;核心C，胰岛 分离和免疫组织病理学核心，M. Solimena，PI.

The present application is for new funding of a program project grant on the Pathogenesis and Prevention of Autoimmune Diabetes. The purpose of this funding is to allow four investigators who have worked together in the past to continue to do in the future. The program consists of four projects supported by three cores. the projects are as follows: Project 1: C.A. Janeway, PI. This project focuses on CD8 T cells that can transfer acute diabetes to NOD mice. These CD8 cloned T cells lines enter the islets in three hours and cause diabetes in all mice tested. We will study their homing, construct a TCR transgenic mouse, and identify the beta cell antigen they detect. Project 2: R.A. Flavell, PI. This project is designed to analyze tolerance in models using normal and NOD transgenic mice, to ask if there is a generalized defecting tolerance in the NOD mice, and to determine its mechanism. Project 3: A.C. Hayday, PI. This project will examine the role of the autoantigen glutamic acid decarboxylase (GAD) in NOD mice. We have observed strong promotion of insultis and some increase in diabetes in these mice. The aim of the project is to study this acceleration, using TCR transgenes specific for GAD. Project 4: RS.Sherwin, PI. This project is mainly focused on the characterization of insulin-specific protective T cell clones. Their mechanism of action and their development will be characterized using TCR transgenics, hopefully leading to a vaccine. The four projects are supported by three core facilities: Core A, Administrative Core, C. Janeway PI; Core B, Animal core, Fs. Wong, PI; Core C, Islet Isolation and Imunohistopathology Core, M. Solimena, PI.