Autoimmune Mouse Core

这项计划拨款由四个综合项目组成：项目1(Pi Jenkins)使用MHC II四聚体试剂在体内分析外周耐受以识别糖尿病患者和糖尿病小鼠的自身反应性CD4+T细胞，项目2(Pi Mueller)无能T细胞的功能特征。项目3(Pi Hogquist)使用一种新的小鼠报告程序定义多克隆群体在健康和疾病中的自我反应性，项目4(PI Mescher)调查CD8+T细胞和关键的第三信号细胞因子在1型糖尿病发病过程中的作用。每个项目都需要特定的小鼠品系，四个核心中的三个需要自发的糖尿病监测、病理分析和与糖尿病特别相关的动物护理。这项分析将包括通过标准的H&E检查胰岛炎症，并辅之以先进的技术，包括特定细胞类型的免疫荧光，以及胰腺和胰腺淋巴结的流式细胞术。这个核心非常适合进行这些研究，因为相同的技术和类似的分析已经由Fife博士进行了11年(1-8)。 自身免疫小鼠核心的主要作用包括： A)为自身免疫实验提供具有成本效益的动物护理和在NOD背景下培育NOD、B6.g7和基因敲除和转基因品系。自发性糖尿病的发展使常规饲养变得复杂，需要额外的关注，以及群体整合，最大限度地减少冗余和动物成本。 B)提供核心小鼠的糖尿病监测和糖尿病管理。如有必要，将为核心维持的糖尿病小鼠品系提供常规的自发性糖尿病筛查和胰岛素治疗。差异基因敲除或转基因小鼠可能会加速糖尿病，因此可能需要专门的护理。为了产生足够数量的计时糖尿病小鼠，必须维持和协调大的队列，以提供足够和一致的实验小鼠。 C)为实验小鼠提供糖尿病监测、治疗和组织采集。核心将监测

This program grant consists of four integrated projects: Project 1 (PI Jenkins) Analysis of peripheral tolerance in vivo to identify autoreactive CD4+ T cells from diabetic human patients and diabetic mice using MHC II tetramer reagents, Project 2 (PI Mueller) Functional characterization of anergic T cells. Project 3 (PI Hogquist) to define the self-reactivity of polyclonal populations in health and disease using a novel mouse reporter, and Project 4 (PI Mescher) to investigate the role for CD8+ T cells and critical third signal cytokines during the initiation of type 1 diabetes. Each project requires specific mouse lines and three of the four cores require spontaneous diabetes monitoring, pathological analysis and animal care specifically relevant for diabetes. This analysis will consist of insulitis by standard H&E, and assistance with advanced techniques including immunofluorescence of specific cell types, and flow cytometry from pancreas and pancreatic lymph nodes. This core is ideally suited to conduct these studies because identical techniques and similar analysis have been carried out for >11 years by Dr. Fife (1-8). The principle roles ofthe Autoimmune Mouse Core include: A) Provide cost effective animal care and breeding of NOD, B6.g7 and genetic knockout and transgenic lines on the NOD background for autoimmune experimentation. Development of spontaneous diabetes complicates routine breeding and requires additional attention as well as colony consolidation minimizes redundancy and animal costs. B) Provide diabetes monitoring and diabetes management of core mice. Routine spontaneous diabetes screening and insulin therapy will be provided as necessary for diabetic mouse strains being maintained by the core. Differential genetic knockout or transgenic mice can accelerate diabetes and therefore specialized care may be required. In order to generate sufficient numbers of timed diabetic mice, large cohorts must be maintained and coordinated to provide sufficient and consistent experimental mice. C) Provide diabetes monitoring, treatment, and tissue harvesting of experimental mice. The core will monito