T cell responses and cardiac transplantation in infancy

婴儿期 T 细胞反应和心脏移植

• 批准号: 7124860
• 负责人: Jeffrey L Platt
• 金额: $ 35.48万
• 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: 2005-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7124860
• 关键词: Macaca fascicularis; T cell receptor; T lymphocyte; autoantibody; autoimmunity; clinical research; heart transplantation; histocompatibility; human subject; human therapy evaluation; immune response; immunosuppressive; infant human (0-1 year); leukocyte activation /transformation; leukocyte depletion therapy; longitudinal human study; microarray technology; outcomes research; patient oriented research; polymerase chain reaction; preschool child (1-5); therapy adverse effect; thymectomy; transplantation immunology

Those who receive a cardiac transplant in the early months of life typically are typically subjected to thymectomy and their T cells are depleted with anti-T cell antibodies. These treatments and the ongoing immunosuppression with which the patients are treated profoundly change the T cell compartment. For example, few recent thymic emigrants are found in the blood and the T cell receptor repertoire is notably contracted. Despite these changes, infants with cardiac transplants do not exhibit the manifestations typical of severe immunodeficiency. The well being of these patients presumably occurs because the residual T cells undergo compensatory proliferation and functional changes. Those participating in this project will study patients who underwent cardiac transplantation early in life and patients who received non-transplant cardiac surgery and hence thymectomy to determine how the repertoire and function of the T cell compartment is changed, what implications these changes have for the well being of the patient (such as viral load and autoimmunity), and whether surgical and medical manipulations might be undertaken to prevent or reverse these changes. Controls will include transplant recipients with intact thymus, subjects with thymectomy but no transplant, and normal individuals of the same age. The research will establish patients with cardiac transplantation early in life or non-transplant cardiac surgery as a standard model for compensatory changes in the T cell compartment. The patients studied will be through collaboration with Dr. West (Project 1); analysis of T cell responses, particularly T cell dependent B cell responses and autoimmunity will be through collaboration with Dr. Cascalho (Project 2); and testing of therapeutic regimens will be in collaboration with Dr. Zhong (Project 4).

那些在生命最初几个月接受心脏移植的人通常会接受胸腺切除，他们的T细胞被抗T细胞抗体耗尽。这些治疗和正在进行的免疫抑制治疗深刻地改变了T细胞隔间。例如，在血液中很少发现最近的胸腺移行者，T细胞受体谱系明显收缩。尽管有这些变化，接受心脏移植的婴儿并没有表现出严重免疫缺陷的典型表现。这些患者的健康状况可能是因为残留的T细胞经历了代偿性增殖和功能变化。参与这个项目的人将研究生命早期接受心脏移植的患者和接受非移植心脏手术并因此接受胸腺切除术的患者，以确定T细胞室的谱系和功能是如何变化的，这些变化对 患者的健康状况(如病毒载量和自身免疫)，以及是否可以采取手术和医疗操作来防止或逆转这些变化。对照组将包括胸腺完整的移植受者、接受胸腺切除但不进行移植的受试者，以及同龄的正常人。这项研究将建立生命早期接受心脏移植或非移植心脏手术的患者作为T细胞室代偿性变化的标准模型。研究的患者将通过与West博士合作(项目1)；T细胞反应，特别是T细胞依赖B细胞反应和自身免疫的分析将通过与Cascalho博士合作(项目2)；治疗方案的测试将与钟博士合作(项目4)。