Cardiac Transplantation in Infancy

婴儿期心脏移植

• 批准号: 7253336
• 负责人: Jeffrey L Platt
• 金额: $ 122.47万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-20 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7253336
• 关键词: Cardiac; Transplantation; Infancy

DESCRIPTION (provided by applicant): This program explores the implications for the immune system of cardiac transplantation in infancy. Cardiac transplantation corrects the devastating physiology of severe congenital heart disease and cardiomyopathy, but it may have a profound and heretofore unrecognized impact on the immune system. The patient is subjected to removal of the thymus and depletion of T cells, and thus might develop defects in T cell and T cell dependent B cell responses. Because the transplant is performed early in life, the recipient may develop spontaneous tolerance to the antigens it carries. And, having few memory lymphocytes, the young infant may be ideally suited for deliberate efforts to induce tolerance. This program will explore these and other implications of cardiac transplantation in the young. In Project 1 "Immunology of cardiac grafts in infants," the questions of whether tolerance to blood group or major histocompatibility antigens arises spontaneously following transplantation and whether the graft becomes accommodated will be addressed. In Project 2 "B cell responses and cardiac transplantation in infancy," the questions of whether patients who receive cardiac transplants in infancy can mount normal T cell independent and T cell dependent B cell responses, including responses to vaccines, and whether these responses can be improved by modifying the regimen or the immunogen will be addressed. In Project 3 "T cell responses and cardiac transplantation in infancy," the questions of whether thymectomy and T cell depletion cause changes in the structure or function of the T cell compartment, and whether these changes can be reversed by various measures will be addressed. In Project 4 "Toward cardiac allograft tolerance in newborn monkeys" non-human primates will be studied to determine whether tolerance to blood group or MHC antigens arises spontaneously, and whether manipulations of the recipient, such as thymus transplantation, can improve immune competence. The program will be supported by an Administrative Core (Core A), which will organize the sharing of data and communication between members of the projects and the Internal and External Advisory Committees and interactions with the parent Institute. The program will be supported by a Laboratory Core (Core B), which will perform analysis of lymphocyte receptor diversity, viral load, auto-antibody levels and review of pathologic specimens common to the various projects. Program Project Facility, Administrative Core, and Laboratory Core: Mayo Clinic, Rochester, Minnesota Project 1: Immunology of cardiac grafts in infants, The Hospital for Sick Children, Toronto, Canada Project 2: B cell responses and cardiac transplantation in infancy, Rochester, Minnesota Project 3: T cell responses and cardiac transplantation in infancy, Rochester, Minnesota Project 4: Toward cardiac allograft tolerance in newborn monkeys, The University of Western Ontario London, Ontario, Canada

描述（由申请人提供）：该项目探讨了婴儿期心脏移植对免疫系统的影响。心脏移植可以纠正严重先天性心脏病和心肌病的破坏性生理机能，但它可能对免疫系统产生深远且迄今为止未被认识到的影响。患者的胸腺被切除，T 细胞被耗尽，因此可能会出现 T 细胞和 T 细胞依赖性 B 细胞反应缺陷。由于移植是在生命早期进行的，因此接受者可能对其所携带的抗原产生自发耐受。而且，由于记忆淋巴细胞很少，小婴儿可能非常适合刻意努力诱导耐受性。该计划将探讨年轻人心脏移植的这些和其他影响。在项目1“婴儿心脏移植物的免疫学”中，将解决移植后对血型或主要组织相容性抗原的耐受是否自发出现以及移植物是否适应的问题。项目2“婴儿期B细胞反应和心脏移植”将解决婴儿期接受心脏移植的患者是否能够产生正常的T细胞非依赖性和T细胞依赖性B细胞反应，包括对疫苗的反应，以及这些反应是否可以通过修改治疗方案或免疫原来改善的问题。项目3“婴儿期T细胞反应和心脏移植”将解决胸腺切除和T细胞耗竭是否会导致T细胞区室结构或功能发生变化，以及这些变化是否可以通过各种措施逆转的问题。在项目4“新生猴子心脏同种异体移植耐受”中，将对非人类灵长类动物进行研究，以确定对血型或MHC抗原的耐受是否自发产生，以及对受体的操作（例如胸腺移植）是否可以提高免疫能力。该计划将得到行政核心（核心 A）的支持，该核心将组织项目成员与内部和外部咨询委员会之间的数据共享和沟通，以及与上级研究所的互动。该计划将得到实验室核心（核心B）的支持，该实验室将进行淋巴细胞受体多样性、病毒载量、自身抗体水平的分析以及对各个项目共有的病理标本的审查。项目设施、行政核心和实验室核心：梅奥诊所，明尼苏达州罗彻斯特 项目 1：婴儿心脏移植免疫学，加拿大多伦多病童医院 项目 2：婴儿期 B 细胞反应和心脏移植，明尼苏达州罗彻斯特 项目 3：婴儿期 T 细胞反应和心脏移植，明尼苏达州罗彻斯特 项目 4：迈向心脏同种异体移植耐受 新生猴子，西安大略大学，加拿大安大略省伦敦