Cellular immunosenescence in F344 rats: decline in responsiveness to phytohemagglutinin involves changes in both T cells and macrophages

Spleen cells from F344 male rats showed decreased DNA synthetic responsiveness [( 3H]thymidine incorporation) with age to the T cell mitogen phytohemagglutinin (PHA). Decreased proliferative responses were associated with decreased production of interleukin-2 (IL-2) and could be partially restored by providing exogenous IL-2. Responses of spleen cells from aged rats could also be enhanced by removal of Sephadex G-10 adherent cells. Furthermore, co-culture of adherent cell-containing spleen cells from aged rats with nonadherent spleen cells from young rats resulted in suppression of responses. Purified peritoneal exudate macrophages (PEM) from aged rats showed potent regulatory effects on PHA responses of young and old nonadherent spleen cells resulting in suppression above 2.5% macrophage/nonadherent spleen cell ratios. PEM from young rats enhanced the response of young T cells but failed to affect the response of aged T cells. T cell proliferation in the presence of prostaglandin (PGE1) showed age-dependent differences in regulation such that at 10(-6) to 10(-7) M young responses were enhanced and old responses were suppressed. These results suggest that decreased responsiveness of T cells to PHA with age is a complex phenomenon involving changes in both production of regulatory mediators by T cells (IL-2) and macrophages (PGE) as well as changes in T cell responsiveness to these signals.