Human Translation and Verification

CORE D- Abstract Increased susceptibility to infectious disease is the most prominent consequence of aging of the immune system. In addition to generating basic knowledge, Projects 1-3 of the “Thymic and peripheral aspects of T cell aging and rejuvenation” Program Project (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 old 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. Core D will also combine treatments from different projects, as appropriate, to synergistically increase T cell production and improve their maintenance in secondary lymphoid organs. 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 with stringent testing of a full spectrum of peripheral immune functions and protective immunity following T cell rejuvenation in old mice. Thereby, the Core will deliver rigorous preclinical data to enable translational rejuvenation efforts in humans.