B cell reaponses and cardiac transplantation in infancy

婴儿期 B 细胞反应和心脏移植

基本信息

批准号：
7474546
负责人：
MARILIA Isabel CASCALHO
金额：
$ 34.05万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-20 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7474546
关键词：
Affinity Antibodies Antibody Formation Antigens Autoantibodies B cell repertoire B-Lymphocytes C57BL/6 Mouse CD4 Positive T Lymphocytes Cardiac Cardiac Surgery procedures Cause of Death Cell Maintenance Cell physiology Cells Child Collaborations Contracts Defect Depressed mood DiGeorge Syndrome Disease Evaluation Financial compensation Generations Genetic Variation Goals Heart Transplantation Helper-Inducer T-Lymphocyte Host Defense Immunity Immunization Immunoglobulin Class Switching Immunoglobulin G Immunoglobulin M Immunoglobulin Switch Recombination Immunosuppression Infection Knowledge Lead Life Lymphoid Macaca fascicularis Maintenance Memory Memory B-Lymphocyte Molecular Morbidity - disease rate Mus Mutate Mutation Organ Organism Patients Population Production Property Proteins Receptors, Antigen, B-Cell Research Research Personnel Residual state Risk Somatic Mutation Syndrome T-Cell Depletion T-Lymphocyte TNFRSF5 gene TNFSF5 gene Testing Therapeutic immunosuppression Thinking Thymectomy Time Transplant Recipients Transplantation Vaccination Virus design human subject improved infancy insight juvenile animal mortality neutralizing antibody pathogen precursor cell prevent programs repaired response thymic aplasia

项目摘要

The overall goal of this project is to determine whether recipients of cardiac transplants in infancy treated with thymectomy, transient T cell depletion and immunosuppression develop defects in the B cell compartment. In these children, compensation of the T cell compartment for the lack of new T cell production and transient T cell depletion may cause a severely contracted T cell repertoire and altered T cell function. Since production of antibodies to protein antigens and B cell memory responses require T cell help, these changes could modify the ability of the B cell compartment to attend to host defense and to regulate auto-immunity. The research proposed in this project will explore whether altered functional properties of the T cell compartment brought about by thymectomy (in non transplanted subjects of cardiac surgery) and T cell depletion and immunosuppression (in recipients of cardiac transplants in infancy) impair T cell-dependent and T cell independent antibody responses, the generation and/or maintenance of B cell memory, B cell receptor diversity and autoantibody production. These studies will be the first to systematically analyze B cell responses in recipients of cardiac transplants in infancy and will produce new fundamental knowledge and insights into how host defense can be improved, in part through the design of more efficient immunization. The project will study patients with cardiac transplants and non-transplant cardiac surgery early in life through collaboration with Project 1. To investigate the mechanisms by which thymectomy, T cell depletion, immunossupression and cardiac allotransplantation may depress B cell responses and to test strategies to improve B cell memory responses, the project will study mice (C57BL/6). The evaluation of the B cell responses will involve collaborations with Project 3 for determining T cell "help" competency, and with Project 4 to analyze B cell responses in cynomolgus monkeys.

该项目的总体目标是确定接受胸腺切除术、瞬时 T 细胞耗竭和免疫抑制治疗的婴儿期心脏移植受者是否会出现 B 细胞区室缺陷。在这些儿童中，T 细胞区室对新 T 细胞生成的缺乏和短暂的 T 细胞耗竭的补偿可能会导致 T 细胞库严重收缩和 T 细胞功能改变。由于蛋白质抗原抗体的产生和 B 细胞记忆反应需要 T 细胞的帮助，这些变化可能会改变 B 细胞区室参与宿主防御和调节自身免疫的能力。该项目提出的研究将探讨胸腺切除术（心脏手术的非移植受试者）和 T 细胞耗竭和免疫抑制（婴儿期心脏移植受者）引起的 T 细胞区室功能特性的改变是否会损害 T 细胞依赖性和 T 细胞独立的抗体反应、B 细胞记忆的生成和/或维持、B 细胞受体多样性和自身抗体的产生。这些研究将是第一个系统分析心脏移植受者 B 细胞反应的研究。在婴儿期进行移植，并将产生关于如何改善宿主防御的新的基础知识和见解，部分通过设计更有效的免疫接种。该项目将通过与项目 1 合作，研究生命早期接受心脏移植和非移植心脏手术的患者。研究胸腺切除术、T 细胞耗竭、免疫抑制和心脏同种异体移植可能抑制 B 细胞反应的机制，并测试改善策略B细胞记忆反应，该项目将研究小鼠（C57BL/6）。 B 细胞反应的评估将涉及与项目 3 合作确定 T 细胞“帮助”能力，并与项目 4 合作分析食蟹猴的 B 细胞反应。