CORE--MORPHOLOGY FACILITY

形态核心设施将为计划项目提供标准化的形态和免疫组织化学分析，这些组织是在存在或不存在病毒感染的情况下从耐受宿主获得的。项目1将使用核心服务对接受同种异体移植并感染各种病毒病原体的小鼠的基本安全性和耐受性进行研究。项目2将利用同种异体T细胞受体转基因模型系统，在感染了病毒病原体的耐受正常小鼠中，利用Core研究同种异体移植物的宿主免疫反应。项目3将使用Core研究自身免疫的自发性糖尿病NOD小鼠的嵌合体和胰岛移植，在存在和不存在病毒感染的情况下，通过一种新的方法诱导耐受。每个项目在设计上都需要大量高质量的组织学分析，以评估移植物排斥反应、移植物存活率，以及在项目3中，移植物抗宿主病(GVHD)。核心将由一位具有委员会认证的病理学家指导，该病理学家在解释临床病理标本方面具有丰富的经验。他的参与旨在为所有项目提供对关键形态数据的一致、高标准的解释。中心还将提供在组织学技术和免疫细胞化学分析方面训练有素的技术人员。在个别项目的初步成果部分、本提案的附录以及该计划所附的几份提交的手稿中可以找到拟议核心成员生成的数据的例子。由一位在监督中央服务设施方面有经验的病理学家指导，将形态研究集中在一个核心，旨在促进合作研究，同时消除每个项目单独开发关键技术的需要。除了传统的组织学、组织冷冻、切片和固定外，核心还将为激素阳性细胞的定位、热诱导表位抗原恢复、用于鉴定细胞表型或细胞因子的免疫过氧化物酶程序、原位杂交、质量控制程序和发育分析提供免疫组织化学。

The Morphology Core Facility will provide the Program Project with standardized morphological and immunohistochemical analyses of tissues obtained from tolerized hosts in the presence or absence of virus infection. Project #1 will use Core services for studies of the basic safety and durability of tolerance in mice given allografts and infected with various viral pathogens. Project #2 will use the Core for studies of the host immune response to allogeneic grafts in tolerant normal mice infected with viral pathogens, using allospecific T cell receptor transgenic model systems. Project #3 will use the Core for studies of chimerism and islet grafts in autoimmune, spontaneously diabetic NOD mice, treated by a new method to induce tolerance, in the presence and absence of viral infection. Each Project will by design require a large number of high- quality histological analyses for evaluation of graft rejection, graft survival, and, in Project 3, graft versus host disease (GVHD). The Core will be directed by a board-certified pathologist with extensive experience in the interpretation of clinical pathological specimens. his participation is designed to provide all projects with a consistent, high standard of interpretation of critical morphological data. The Core will also provide technicians who are well trained in both histology techniques and immunocytochemical assays. Examples of the data generated by members of the proposed Core will be found in the Preliminary Results Sections of the individual Projects, the Appendix to this Proposal, and in several of the Program's appended submitted manuscripts. The centralization of the morphologic studies in a Core directed by a pathologist with experience in supervising central service facilities is designed to facilitate collaborative research while obviating the need for each project to develop key techniques individually. In addition to conventional histology, tissue freezing, sectioning and fixing , the Core will provide immunohistochemistry for localization of hormone positive cells, heat induced epitope antigen retrieval, immunoperoxidase procedures for the identification of cell phenotype or cytokines, in situ hybridization, quality control procedures, and developmental assays.