T Cell Maturation and Thymic Activity in the Aged

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EXCEED THE SPACE PROVIDED. Aging results in well documented changes in the immune system, including a dramatic increase in the proportion of memory T cells and a corresponding decrease in the naive T cell population, although the absolute number of T cells does not change. The end result of this shift may be reflected in the increased risk of cancer and infectious disease in the elderly. The goal of this program has been to improve immunoreactivity in the aged by manipulating the subset distribution of T cells, and testing the hypothesis that age-related alterations in immunological activity result from this shift in representational frequency of the functionally distinct naive and memory T cells. The immediate past funding period looked at bone marrow transplantation as a way to alter the ratio of memory and naive T cells in the aged host. The findings form the basis for the hypothesis to be tested in this period; the shift from a naive to a memory-enriched T cell population associated with advancing age is due to altered T lymphocyte homeostasis resulting from changes in the microenvironment. Three specific aims will address this hypothesis. First we will identify the age-associated changes in the microenvironment that affect T cell homeostasis. Secondly, we will determine how T lymphocyte lifespan, expansion and maturation respond to aging of the microenvironment. Lastly, we will manipulate the microenvironment using the information gained in the first two aims, to improve T cell function and overall immune reactivity in the aged. The intent of these studies is to improve our knowledge of T cell function in aging, with the ultimate goal of strengthening immune reactivity in aged individuals and achieving better immunoreconstitution following chemotherapy, bone marrow transplantation, or antiviral treatment for AIDS. PERFORMANCE SITE ========================================Section End===========================================