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

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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.