Core D: Thymic and peripheral Aspects of T cell Aging and Rejuvenation

核心 D：T 细胞衰老和再生的胸腺和外周方面

• 批准号: 9755307
• 负责人: Megan J Smithey
• 金额: $ 16.42万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9755307
• 关键词: Aging; Animals; Antibodies; Antibody Formation; Arizona; B-Lymphocytes; Biological Assay; Biological Models; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; Cell Aging; Cell Maintenance; Cell physiology; Cellularity; Communicable Diseases; Competence; Cost Savings; Data; Data Analyses; Data Collection; Elderly; Emigrant; Ensure; Failure; Female; Generations; Goals; Human; Human Resources; Immune; Immune response; Immune system; Immunity; Immunology procedure; Individual; Intervention; Knowledge; Laboratories; Maintenance; Measures; Mediating; Modeling; Monitor; Morbidity - disease rate; Mus; Neuraxis; Output; Pathway interactions; Peripheral; Predisposition; Procedures; Program Research Project Grants; Protocols documentation; Quality Control; Rejuvenation; Research; Research Personnel; Resolution; Services; Specimen Handling; Spleen; T cell response; T-Lymphocyte; T-Lymphocyte Epitopes; Testing; Thymus Gland; Time; TimeLine; Tissue Sample; Training; Translating; Universities; Virus Diseases; West Nile viral infection; West Nile virus; adaptive immunity; aged; animal resource; arm; biosafety level 3 facility; experimental study; functional improvement; genetic approach; immune function; improved; in vivo; lymph nodes; male; member; mortality; mouse model; mutant mouse model; pathogen; peripheral blood; pre-clinical; programs; response; sample collection; transcription factor

Core D- Abstract Increased susceptibility to infectious disease is the most prominent repercussion of the aging immune system. In addition to generating basic knowledge, Projects 1-4 of the “Thymic and peripheral aspects of T cell aging and rejuvenation” Program Project Grant (Program) will provide an array of potential rejuvenation strategies. The Immunological Response & Rejuvenation Strategy Monitoring Core (Core D), located at the University of Arizona, will provide the final experimental pipeline for testing those rejuvenation strategies. Specifically, the global objective of Core D is to assess thymic export and peripheral maintenance of naïve T cells following T cell rejuvenation in aged mice, and determine whether such interventions can improve adaptive and protective immunity against viral infection in old mice. The Core will provide dedicated personnel with the appropriate infectious disease expertise to ensure consistency and quality control in the execution of study protocols, application of experimental procedures, and animal observations and data collection necessary to meet the Program's major research objectives. This testing pipeline will not only separate candidate interventions by their efficacy, but will also identify potential stages at which some rejuvenation strategies may fail to translate into improved immune function. The use of rigorous in vivo analysis to track recent thymic emigrants, and immunity in response to West Nile virus, a pathogen that shows disproportionally high morbidity and mortality within the elderly, will provide this Program and its Projects stringent testing of a full spectrum of peripheral immune function and protective immunity following T cell rejuvenation in aged mice. Thereby, the Core will deliver rigorous preclinical data, that, together with the Human-Mouse Timeline (generated by Projects 1-4 and other Cores) will enable translational rejuvenation efforts in humans.

核心D-摘要 对传染病的易感性增加是老龄化最突出的后果 免疫系统除了产生基本知识外，“胸腺和 T细胞老化和复兴的外周方面”计划项目赠款（计划）将 提供了一系列潜在的复兴策略。免疫反应& 复兴战略监测核心（核心D），位于亚利桑那大学，将 为测试这些恢复策略提供最终的实验管道。具体而言是 核心D的全球目标是评估胸腺输出和外周维持 在老年小鼠中T细胞再生后的幼稚T细胞，并确定这是否 干预措施可以提高老年人对病毒感染的适应性和保护性免疫力 小鼠 该中心将提供具有适当传染病专业知识的专门人员 为确保研究方案执行的一致性和质量控制， 实验程序，动物观察和数据收集，以满足 计划的主要研究目标。这条测试管道不仅将候选人 干预措施的有效性，但也将确定潜在的阶段， 策略可能无法转化为改善的免疫功能。使用严格的体内 分析跟踪最近的胸腺移民，免疫反应西尼罗河病毒， 在老年人中表现出高发病率和死亡率的病原体，将提供 该计划及其项目严格测试外周免疫功能的全谱 和老年小鼠T细胞复壮后的保护性免疫。而核心， 严格的临床前数据，与人-小鼠时间轴（由项目生成）一起， 1-4和其他核心）将使人类的翻译复兴努力成为可能。