Conditioned immunosuppression in young versus aged mice: Differences in cells and responses to environmental stimuli lead to altered conditioning in aged animals

Abstract

Aged mice (>20 months of age) show a decreased immune response after antigen challenge compared to their young counterparts. In this study aged mice were also found to show a diminished conditioned immunosuppression after associative learning trials with cyclophosphamide and saccharin, followed by immune stimulation in the presence of saccharin, when compared to young (10 weeks) syngeneic mice. Adoptive transfer experiments in which cells from nonconditioned or conditioned young or aged mice were injected into irradiated conditioned young or aged syngeneic mice (exposed or not exposed to conditioned stimuli) revealed the following: (1) There was an altered responsiveness of normal cells injected into conditioned aged mice (reexposed to cues) compared to the response in young recipients; (2) Cells from conditioned young mice failed to show conditioned immunosuppression on adoptive transfer to irradiated conditioned aged mice; (3) Cells from conditioned aged mice failed to show conditioned immunosuppression on adoptive transfer to irradiated conditioned young mice; (4) The changes seen in spleen cells from conditioned aged mice (relative to similar cells from young mice) were to be found in the T cell population of these animals. These data are consistent with the idea that during aging changes in both the responding cells and the conditioned environment, along with the interaction of these, produce a decreased ability to document conditioned immunosuppression of antibody responses.