Immunopathology Core

核心A的目的是为该计划项目的所有四个项目中的免疫病理学研究提供共同的设施和专业知识。有人可能会质疑在一个主要目标是建立移植耐受性的计划项目中进行病理分析的必要性，因为如果这个目标实现了，那么分析的移植物病理就会很少。然而，很明显，病理分析的指导对于实现我们的目标是必不可少的。这些耐受性协议中的病理分析的主要作用是记录和描述： 1)移植物的状态(浸润性、是否存在急性或慢性排斥反应，包括体液成分) 2)嵌合体状态(细胞类型、分布) 3)方案的全身性影响(毒性、并发症)。 此外，在拟议的研究过程中出现了许多宝贵的机会，这将使 对移植物排斥和接受机制的洞察。特别是，通过大型动物研究中的常规活组织检查，我们有机会： 4)区分导致接受和拒绝的渗透的性质 5)分析移植物是否有预测结果的前驱病变，例如慢性排斥反应。 病理特征将由同一组病理学家对所有研究进行评估和分级，我们认为这是该计划项目的重要资产。只要有可能，抗体和细胞因子探针小组也将具有可比性。这将通过推广新的发现来促进项目之间的交叉受精，并通过比较不同物种和不同器官之间的移植物来深入了解一个项目的结果的一般意义。我们也有一个来自我们之前的移植实验(&gt；5000个样本)的冷冻和石蜡包埋组织的良好注释的组织库，可以用来扩展和完善我们的分析。

The purpose of Core A is to provide common facilities and expertise for the immunopathological studies in all four projects of the Program Project. One might question the need for pathological analysis in a Program Project whose principal goal is the establishment of transplantation tolerance, since, if this goal were achieved, there would be little, if any graft pathology to analyze. However, it is clear that guidance from pathological analysis is essential to achieve our goal. The primary role of the pathological analyses in these tolerance protocols is to document and characterize: 1) The status of the graft (nature of infiltrate, presence of acute or chronic rejection, including humoral component) 2) The status of chimerism (cell type, distribution) 3) The systemic effects of the protocols (toxicity, complications). In addition, many valuable opportunities arise in the course of the proposed studies that will give insights into the mechanisms of graft rejection and acceptance. In particular, with protocol biopsies in the large animal studies we have the opportunity to: 4) Distinguish the nature of the infiltrate that leads to acceptance vs. rejection 5) Analyze grafts for precursor lesions that predict outcome, e.g., chronic rejection. The pathology features will be assessed and graded by the same group pathologists for all studies, which we consider an important asset of the Program Project. The panel of antibodies and cytokine probes will also be comparable, whenever possible. This should promote cross-fertilization among the projects by extension of novel findings and provide insights into the general significance of the results in one project by comparing and contrasting grafts in different species and between different organs. We also have a well annotated tissue bank of frozen and paraffin embedded tissue available from our previous transplantation experiments (>5000 samples), which can be drawn upon to expand and refine our analysis.