MOLECULAR BASIS FOR DECEASED IMMUNE FUNCTION IN AGING HUMANS AND RATS

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It is well established from human and animal studies that there is a general decrease in immune function that occurs with aging. This project focuses on examining the cause(s) for this decline at the molecular level. In particular, we have focused on the activation of T lymphocytes by mitogen. Three T-cell proteins have been examined thus far: interleukin 2 (IL-2), a lymphokine absolutely required for the proliferation of certain T cell populations; IL-2 receptor (IL-2R), the cell surface receptor for IL-2; and interferon gamma, another lymphokine whose regulation is intimately linked to IL-2. Expression of the IL-2 and IL-2R genes in human peripheral blood lymphocytes (PBL) was examined form 13 young and 17 elderly donors. In addition to decreased proliferative capacity, elderly individuals displayed a significant decrease in the amount of IL-2 protein activity and expression of IL-2R relative to younger individuals. These decrease were accompanied by decreased levels of IL-2 and IL-2R specific mRNA. Similar results have been obtained with interferon a gamma in a smaller number of donors. Thus, it appears that decreased induction of all three of these genes upon antigenic stimulation contributes to the diminished T cell function observed in the elderly.