This application is directed at defining the mechanisms at both the cellular and molecular basis which are responsible for the marked decrease in immunological competency that accompanies the aging process. The approach taken in this application is based on the original observation made in our laboratory demonstrating that the capacity to generate IL-2 is markedly deficient in spleen cells of aged C57BL/6 mice and that the in vitro immunological defects of spleen cells of these aged mice can be corrected by supplying IL-2. It is planned to study in depth the underlying mechanism responsible for the deficiency in the ability to generate effective IL-2 in aged animals and its underlying role in the loss of immunological competency during aging. In addition we will determine if the immunoreactivity of aged animals can be restored in vivo with IL-2 and, if so, what are the conditions necessary for such restoration. Initially, we will determine when during the aging process does IL-2 production wane and is there a direct correlation between the ability to generate IL-2 and the loss of immunological competency. Experiments will be carried out to determine if the lesion and the ability to generate IL-2 in aged mice is associated with the underlying effect in IL-1 production. Other experiments will be performed to determine if the function and level of IL-2 receptors are normal in aged mice. The question will also be asked, """"""""is the loss of the capacity to generate IL-2 in aged mice the result of a decrease in the number of IL-2-producing cells or in the amount of Il-2 produced by each cell""""""""? Whether both the recruitment and the expansion of effector cells are affected by the aging process will also be addressed. Other experiments are designed to determine if IL-2 is required for effective expansion of mature suppressor (Ts) cells and, if so, is the in vivo suppressor cell activity compromised in IL-2-deficient aged mice. It will be determined whether our preliminary experiments suggesting that immunological memory is spared during the aging process can be verified and, is so, the underlying cellular and molecular basis will be determined. Finally, we will investigate whether the helper T cells, precursor T cells or effector T cells are affected in cell-mediated lympholysis during the aging process and whether IL-2 plays a direct or indirect role.
