Analysis of the age-related decline in alloreactivity of CD4+ and CD8+ T cells in CBA/RIJ mice.

CD4+ T cells from healthy old CBA/Rij mice were studied for their ability to respond to alloantigens by IL-2 production and proliferation. IL-2 production by these purified cells in response to BALB/c spleen cells was about 4 times lower than the IL-2 production (50 U/ml) by CD4+ T cells from young mice. After stimulation with concanavalin A only a two-fold difference in IL-2 production was found. The extent of proliferation by CD4+ T cells from old mice in response to allogeneic cells was at least 4 times lower than that by the cells from young mice. This difference was not influenced by the addition of IL-2 containing conditioned medium (CM). Proliferative responses by CD8+ T cells were only found after the addition of CM and then the response by cells from old mice was 2-10 times lower than the response by cells from young mice. Limiting dilution analysis of the separate T cell subpopulations showed that these low responses to alloantigens by cells from old mice were only in part due to a decline in the frequency of antigen-specific CD4+ or CD8+ T cells. As far as old CD8+ T cells were concerned, an additional explanation for the low responsiveness was found in a diminished expression of the IL-2 receptor (IL-2R) alpha-chain. However, CD4+ T cells from old mice expressed normal levels of IL-2R alpha-chain. The observation that proliferative responses by CD4+ T cells may be low, despite a normal frequency of antigen-specific cells, an apparently normal IL-2R expression and despite the presence of exogenous IL-2, indicates that CD4+ T cells from old mice are not only impaired in their ability to produce IL-2, but are also impaired in their ability to handle the IL-2 signal.