The human thymus is required for the generation, maturation, and export of T lymphocytes to the periphery where they coordinate adaptive immune responses. Naive T cells are generated via thymopoiesis in early childhood followed by a gradual reduction in thymic function and an age-dependent involution of the functional organ volume beginning in puberty. It is not understood how and whether human naive T cells are maintained in the context of decreasing thymic output throughout life, mainly because studies on human T cell development have been limited to the sampling of peripheral blood. The issue of naive T cell survival and the role of thymic output in repopulation of T cells is of particular relevance in understanding the preservation of an effective immune response in aging individuals. With increasing age, size of the naive T cell pool is affected both by a decrease in thymic export and a transition into effector memory cells following exposure to antigen. We propose here a new approach to study the dynamics of human T cell development and homeostasis by investigating T cell populations in primary and secondary lymphoid tissue isolated from individual organ donors. Results from the proposed study will have implications not only in the field of immunology which pertains to aging but will provide new information of how naive T cells are distributed and maintained in tissues not previously characterized. Furthermore the proposed research will be of relevance to promoting immune responses to new pathogens or vaccines while furthering the understanding of mechanisms for immune dysregulations that can occur with advancing age.
The proposed research will conduct novel studies of human immune cells in tissue sites throughout the body that have not previously been characterized, using a unique tissue resource set up by the research advisor. The results to be obtained and concepts to be learned will yield significant advances in human immunology of aging populations and impact the way we analyze and interpret disease pathologies, design vaccines, and use immunotherapy to treat and cure intractable diseases.
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