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: 7618480
• 负责人: NANCY J HALNON
• 金额: $ 11.64万
• 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/7618480
• 关键词: Acceleration; Address; Affect; Age; Allograft Tolerance; Animal Model; Antibodies; Autoimmune Diseases; B-Lymphocytes; Cardiac Surgery procedures; Cell Aging; Cell Proliferation; Cells; Cellular Immunity; Chemotherapy-Oncologic Procedure; Child; Childhood; Clinical Investigator Award; Consensus; DNA Sequence Rearrangement; Data; Development; Emigrant; Excision; Exhibits; Family; Flow Cytometry; Future; Generations; Heart Transplantation; Humoral Immunities; Immune; Immune system; Immunity; Immunologics; Individual; Infant; Investigation; Investigative Techniques; Length; Life; Longitudinal Studies; Lymphocyte; Lymphopenia; Maintenance; Measures; Molecular; Natural Killer Cells; Operative Surgical Procedures; Organ Transplantation; Patients; Peripheral; Play; Population; Population Heterogeneity; Program Development; Reporting; Research Personnel; Role; Seeds; Solid; T memory cell; T-Cell Receptor; T-Lymphocyte; T-Lymphocyte Subsets; Techniques; Thymectomy; Thymic Tissue; Thymus Gland; Time; Vaccine Antigen; Vaccines; anergy; base; cohort; congenital heart disorder; cytokine; early childhood; experience; immune function; infancy; premature; prospective; reconstitution; response; routine practice; senescence; telomere; young adult

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(申请人提供)：儿童早期免疫成熟期胸腺切除的长期影响尚未被调查。一群患有先天性心脏病的儿童和年轻人正在形成，他们在生命早期就接受了附带胸腺切除术。目前，在外科实践中，对于接受心脏手术的幼儿，切除或保留胸腺还没有达成共识。在历史上，胸腺被认为在儿童时期就开始退化，成年后就失去了功能，因此在心胸外科手术中胸腺切除的常规做法没有禁忌症。然而，更新的研究技术已经允许胸腺活动一直显示到成年，并揭示了胸腺功能对于癌症化疗后的免疫重建和实体器官移植后诱导同种异体移植耐受的必要性。我们假设，在婴儿期的心胸外科手术中，胸腺切除会导致细胞免疫系统的长期变化。基于先前的证据和初步数据，我们建议在不同种族的先天性心脏病儿童和青年人群中进行回顾性和前瞻性的纵向研究，以确定婴儿胸腺切除对外周淋巴细胞池的影响和细胞免疫功能的测量。在K08发展计划的背景下，具体目标如下： 目的1：检测胸腺切除对外周血T淋巴细胞亚群产生和维持的影响。我们将确定关键淋巴细胞群体的大小，并检测过早免疫衰老的参数。 目的：探讨胸腺切除对机体细胞免疫、体液免疫及T细胞受体多样性的影响。将评估儿童疫苗的反应性，并测量效应器T细胞谱系的广度。 这些研究将为研究人员提供经验，这些经验将被应用于未来儿童心脏移植中免疫失调的研究。

项目成果

A Francisella novicida pdpA mutant exhibits limited intracellular replication and remains associated with the lysosomal marker LAMP-1.

新杀弗朗西斯菌 pdpA 突变体表现出有限的细胞内复制，并且仍然与溶酶体标记物 LAMP-1 相关。

• DOI: 10.1099/mic.0.025445-0
• 发表时间: 2009
• 期刊: Microbiology (Reading, England)
• 作者: Schmerk,CrystalL;Duplantis,BarryN;Howard,PerryL;Nano,FrancisE
• 通讯作者: Nano,FrancisE

Characterization of the pathogenicity island protein PdpA and its role in the virulence of Francisella novicida.

致病岛蛋白 PdpA 的表征及其在新杀弗朗西斯菌毒力中的作用。

• DOI: 10.1099/mic.0.025379-0
• 发表时间: 2009
• 期刊: Microbiology (Reading, England)
• 作者: Schmerk,CrystalL;Duplantis,BarryN;Wang,Diana;Burke,RobertD;Chou,AliciaY;Elkins,KarenL;Ludu,JagjitS;Nano,FrancisE
• 通讯作者: Nano,FrancisE