Thymectomy and Immunity in Congenital Heart Disease

先天性心脏病的胸腺切除术和免疫

• 批准号: 6927582
• 负责人: NANCY J HALNON
• 金额: $ 10.56万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6927582
• 关键词: B lymphocyte; T cell receptor; active immunization; cellular immunity; clinical research; congenital heart disorder; cytotoxic T lymphocyte; developmental immunology; flow cytometry; human subject; humoral immunity; immune response; immunosenescence; longitudinal human study; lymphocyte proliferation; natural killer cells; phenotype; polymerase chain reaction; preschool child (1-5); questionnaires; therapy adverse effect; thymectomy

DESCRIPTION (provided by applicant): The long term impact of thymectomy during the period of immunologic maturation in early childhood has not been investigated. A cohort of children and young adults with congenital heart disease is forming in whom incidental thymectomy was performed early in life. There is currently no consensus in surgical practice regarding excising or sparing the thymus in young children undergoing cardiac surgery. Historically the thymus was thought to begin involution in childhood and to be non-functional by adulthood, thus presenting no contraindication to the routine practice of thymectomy during cardiothoracic surgery. Newer investigative techniques, however, have allowed demonstration of thymic activity well into adulthood and revealed the necessity of thymic function for immune reconstitution following cancer chemotherapy and for induction of allograft tolerance following solid organ transplantation. We hypothesize that incidental thymectomy during cardiothoracic surgery in infancy causes long term changes in the cellular immune system. Based on previous evidence and preliminary data we propose both retrospective and prospective longitudinal studies in an ethnically diverse population of children and young adults with congenital heart disease to determine the impact of infant thymectomy on peripheral lymphocyte pools and measures of cellular immune function. In the context of K08 program of development, the specific aims are as follows: Aim 1: To measure effects of thymectomy on the generation and maintenance of the peripheral T lymphocyte populations. We will determine the size of key lymphocyte populations and examine parameters of premature immune senescence. Aim 2: To measure effects of thymectomy on cellular and humoral immunity and T cell receptor diversity. Responsiveness to childhood vaccines will be evaluated and the breadth of the effector T cell repertoire will be measured. These studies will provide the investigator with experience which will be applied to future investigations of immune dysregulation in the context of cardiac transplantation in children.

描述（由申请人提供）：尚未研究在儿童早期免疫成熟期进行胸腺切除术的长期影响。一组患有先天性心脏病的儿童和年轻人正在形成，他们在生命早期进行了偶然的胸腺切除术。目前在外科实践中，对于接受心脏手术的幼儿切除或保留胸腺没有达成共识。历史上，胸腺被认为在儿童时期开始退化，到成年时无功能，因此在心胸外科手术中常规进行胸腺切除术没有禁忌症。然而，较新的研究技术，允许证明胸腺的活动以及进入成年期，并揭示了胸腺功能的必要性，免疫重建后癌症化疗和诱导同种异体移植物耐受后实体器官移植。我们假设婴儿期心胸外科手术中偶然的胸腺切除会引起细胞免疫系统的长期变化。根据之前的证据和初步数据，我们建议对患有先天性心脏病的种族多样的儿童和年轻人群体进行回顾性和前瞻性纵向研究，以确定婴儿胸腺切除术对外周淋巴细胞库和细胞免疫功能测量的影响。 在K08发展计划的背景下，具体目标如下： 目的1：探讨胸腺切除对外周血T淋巴细胞生成和维持的影响。我们将确定关键淋巴细胞群体的大小，并检查过早免疫衰老的参数。 目的2：探讨胸腺切除对机体细胞免疫、体液免疫和T细胞受体多样性的影响。将评估对儿童疫苗的反应性，并测量效应T细胞库的宽度。 这些研究将为研究者提供经验，这些经验将应用于儿童心脏移植背景下免疫失调的未来研究。