Thymectomy and Immunity in Congenital Heart Disease

点击翻译按钮获取中文摘要

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.