IMPACT OF CMV UPON T-CELL AGING AND IMMUNE DEFENSE

CMV 对 T 细胞衰老和免疫防御的影响

基本信息

批准号：
8891346
负责人：
JANKO Z. NIKOLICH
金额：
$ 43.48万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-15 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8891346
关键词：
Acute Address Affect Aging Bone Marrow Cardiovascular Diseases Cardiovascular system Cell Aging Cells Chimera organism Control Locus Cytomegalovirus Cytomegalovirus Infections Defect Development Elderly Etiology Exhibits Genes Goals Health Human Immune Immune response Immune system Immunity Impairment Individual Infection Infectious Agent Inflammation Influenza vaccination Light Link Longevity Lytic Measurement Measures Mediating Memory Molecular Molecular Profiling Monitor Morbidity - disease rate Mus Pathology Population Rejuvenation Residual state Resources Role Sampling Spleen T cell response T memory cell T-Cell Receptor T-Lymphocyte Testing Therapeutic Intervention Transcript Translating Urine Vaccination Viral Virus Virus Shedding West Nile virus Youth age related cell age cohort constriction cost immune function improved influenzavirus insight latent infection lymph nodes reactivation from latency research study response

项目摘要

DESCRIPTION (provided by applicant): The cytomegalovirus (CMV) has been associated to T-cell aging, impaired immunity, reduced residual lifespan and increased morbidity of cardiovascular diseases. It was recently shown by our group that old mice, infected in youth with CMV, but not other viruses, exhibit defects in immune responsiveness to third-party infections, and alterations in na�ve T cell receptor (TCR) repertoire. Yet, the precise mechanism by which CMV impairs na�ve T cell responses remains incompletely understood. This proposal seeks to define the cost, if any, of persistent CMV infection on host immune function (and lifespan) in aging and to begin to define ways to intervene against negative effects of CMV in aging. Lifelong CMV infection could adversely impact the development of new immune responses (i) by precipitating additional loss of na�ve T cell diversity; and (ii) by interference of inflated, CV-specific effector memory (EM) T cells with na�ve T cell responses against new infection. Further, improved control of CMV and/or reduction of CMV-specific EM accumulation could be beneficial for immune defense. The aims will assess (i) the role of CMV in constriction of T cell receptor (TCR) repertoire and immune defense in mice; (ii) Inhibition of protective immunity by CMV and/or by CMV-specific T cells; and (iii) whether improved CMV control determine human immune responsiveness to vaccination,

描述（由适用提供）：巨细胞病毒（CMV）与T细胞衰老，免疫学受损，残留寿命降低和心血管疾病发病率增加有关。我们的小组最近表明，在CMV青年中感染但不感染其他病毒的老鼠在对第三方感染的免疫调查中存在缺陷，以及中殿T细胞受体（TCR）曲目的改变。然而，CMV撞击中含在T细胞反应的精确机制尚不完全理解。该提案旨在定义衰老中宿主免疫功能（和寿命）持续性CMV感染的成本（如果有的话），并开始定义方法以干预CMV对CMV的负面影响。终身CMV感染可能会通过促进中Have T细胞多样性的额外丧失而对新免疫反应（i）产生不利影响；（ii）通过干扰膨胀的，CV特异性效应子记忆（EM）T细胞，其中含T细胞反应针对新感染。此外，改善了CMV的控制和/或减少CMV特异性EM积累可能对免疫诱变有益。目的将评估（i）CMV在小鼠中T细胞受体（TCR）曲目和免疫反弹的收缩中的作用；（ii）CMV和/或CMV特异性T细胞抑制受保护的免疫力；（iii）改进的CMV控制是否确定了人类对疫苗接种的免疫反应，