Homeostasis of Mature T Cells in the Aged

Scripps Research Institute, La Jolla CA

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Abstract

Aging is associated with a decline in the repertoire and the functional capacity of the mature T cells. The reduced ability of the aged cellular immune system to respond to new antigenic challenges appears to be largely a result of attrition in the size of the naive T cell pool and the decline in the responsiveness of the antigen-specific T cells. Exactly what causes the reduction of the naive T cell pool is not known, but is generally believed to be a combination of decreased thymic output of newly generated T cells coupled with life-long conversion of naive cells into memory cells from exposure to antigens. Other mechanisms, however, are possible, especially when one considers that T cells are subject to constant regulation by homeostatic mechanisms that regulate the overall size and the composition of the T cell pool. In this respect, we and others have recently begun to identify the essential factors that regulate the homeostasis of naive and memory T cells. To determine whether the decline in the naive cells in the aged is partly caused by age-related changes in the factors that control T cell homeostasis, we propose following three areas of investigation. First, the host environment of the aged will be tested for their capacity to support homeostasis of naive and memory T cells. Second, the expression of factors that regulate homeostasis of naive T cells will be measured in aged mice. Third, the possibility of restoring the naive T cell pool in old mice through manipulation of the homeostatic factors will be tested.