IMMUNOPATHOGENESIS OF CHRONIC CARDIAC GRAFT REJECTION

我们提出了一个综合的、多学科的基础和 临床研究的总体目标是确定T细胞的作用 细胞在心脏移植慢性排斥反应发病机制中的作用 开发预防慢性排斥反应的新方法，方法是诱导、 受体T细胞，对同种异体心脏移植的耐受性。这 将通过评估捐赠者骨髓输注是否 将预防或减轻人类移植物动脉硬化(GA)的严重程度 通过增加微嵌合体和诱导抗原- 特定容忍度。 本计划项目基于以下领域的广泛的最先进专业知识 年微生物学和免疫学系人类T细胞免疫学 坦普尔大学医学院和一个广泛而非常 坦普尔成功的成人心脏移植临床计划 大学医院，这是美国最繁忙的。七十 1994年，坦普尔大学健康中心进行了6例心脏移植手术 科学。截至1995年10月12日，已有65例心脏移植手术 已经完成了。本计划项目由研究项目组成： 1.T细胞在慢性排斥反应发病机制中的作用 细胞因子在GA发生发展中的作用是 地址。3.第三个研究项目的目标是确定 供者骨髓的使用是预防还是减少 心脏移植受者GA的发生率和严重程度及其增加 微嵌合体。这些互动研究得到了一项临床研究的支持 移植核心与行政核心。《临床》 移植核心公司包括与C.Ricordi博士的财团安排 迈阿密大学医学院。

We propose an integrated, multi-disciplinary research program of basic and clinical research with an overall objective to determine the role of T cells in the pathogenesis of chronic rejection of cardiac allografts and to develop new approaches for prevention of chronic rejection by inducing, in athe T cells of the recipient, tolerance to the cardiac allograft. This will be accomplished by evaluating whether infusion of donor bone marrow will prevent or reduce the severity of graft arteriosclerosis (GA) in human cardiac allografts by increasing microchimerism and inducing antigen- specific tolerance. This Program Project is based on extensive stat e-of-the-art expertise in human T-cell immunology in the Department of Microbiology and Immunology of Temple University School of Medicine and on an extensive and very successful clinical adult heart transplantation program at Temple University Hospital, which is the busiest in the United States. Seventy six heart transplants were performed in 1994 at Temple University health Sciences. As of October 12, 1995 sixty five heart transplants have already been performed. This Program Project is comprised of Research Projects: 1. The role of T cells in the pathogenesis of chronic rejection is addressed, 2. The role of cytokines in the development of GA is addressed. 3. The objective of the third Research Project is to determine whether administration of donor bone marrow prevents or reduces the incidence and severity of GA in cardiac transplant recipients and increases microchimerism. These interactive studies are supported by a Clinical Transplantation Core and an Administrative Core. The Clinical Transplantation Core includes a consortium arrangement with Dr. C. Ricordi of the University of Miami, School of Medicine.