Core A: Administrative Core Project Summary Our understanding of how human adaptive immune responses are initiated, evolve over time, and become durable have been shaped largely, although not exclusively, by what we have learned from measuring B and T cells in the blood following immune perturbations with pathogens, vaccines and immune-modulating drugs. While longitudinal analyses can be performed with blood samples, it is only possible to assess the recirculating immune cells and we know that many antigen-experienced “memory” B and T cells rarely recirculate and reside in peripheral and lymphoid tissues. Recent studies in animals reveal that immune memory cells in tissues play important early roles in immune protection at barrier sites. The generation and maintenance of these cells are controlled by different mechanisms and these tissue-residing memory cells are endowed with distinct phenotypic, molecular, and functional programs. Although it is difficult to study human tissue-residing immune cells, the elegant studies that have been done confirm that studying immune cells in tissues reveals additional complexity that is not always captured in peripheral blood. However, to date, most human studies in peripheral tissues have not evaluated the evolution or durability of antigen specific B and T cell responses in the face of a continuously changing microenvironment and/or ongoing antigen exposure. This gap in knowledge limits our ability to identify appropriate modalities to boost and maintain protective immune cells within peripheral tissues and to prevent the development and persistence of potentially pathogenic immune cells that contribute to tissue damage. This U19 addresses the knowledge gap by characterizing immune memory cells that reside in tissue samples derived from transplant patients. The unifying goals of the three U19 projects are to better understand the evolution of human immune memory responses in tissue and blood and to characterize the factors that contribute to the persistence and durability of human memory T and B cells. To meet these goals, investigators with complementary expertise in B and T cell biology, infectious disease, transplantation and autoimmunity will work together to methodically interrogate the memory B and T cell compartments in transplanted kidney, uterus and lung. The major objective of Core A is to provide financial, scientific and regulatory oversight and administrative support for the overall Program as well as the individual projects and cores. We will achieve this objective by: (i) supporting the scientific progress of the projects and cores, organizing the monthly research in progress meetings and interfacing with the project and core team members to ensure needs are met; (ii) organizing scientific interactions such as the annual retreat with the scientific advisory board, and the annual Cooperative Centers on Human Immunology investigator meeting; (iii) providing financial oversight and administrative ...