Age-related decline in humoral immunity caused by the selective loss of T H cells and decline in cellular immunity caused by the impaired migration of inflammatory cells without a loss of T DTH cells in SAMP1 mice

Abstract

We investigated the cellular basis of the age-related decline in antibody (Ab) and delayed-type hypersensitivity (DTH) responses to sheep red blood cells (SRBC) in vivo in short-lived senescence-accelerated mouse (SAM) P1. In SAMP1 mice, age-related decreases in CD4 + T cells in the peripheral blood occurred earlier than in control mice and occurred in parallel with the age-related decline in Ab and DTH responses. In addition, the involution of the thymus was faster. The injection of thymic T cells from young mice before sensitization completely restored the Ab responses in aged SAMP1 mice. These data suggest that the age-related decline in Ab response is due to the age-related early loss of helper-T (T H) cells. On the other hand, the local transfer of spleen cells from sensitized aged donors into the footpads of naive syngeneic recipients evoked strong DTH responses, demonstrating the existence of DTH-mediating T (T DTH) cells in the spleens of aged SAMP1 mice. Moreover, the local injection of naive spleen cells from young donors, together with the antigen, into the footpads caused DTH responses in sensitized aged recipients. These findings indicate that T DTH cells were induced and were able to migrate and function as effector cells in aged mice. When naive spleen cells from aged donors were injected locally into the footpad, they restored the DTH response in aged mice, but this effect did not work if the cells were injected intravenously. This demonstrates that the inflammatory cells of the aged mice were able to work at the local site, but could not migrate there. The intravenous injection of naive spleen cells from young donors restored the DTH response in aged mice, suggesting that the endothelial cells of aged mice were not impaired and permitted the inflammatory cells to migrate into the extravascular tissues. Thus, although the age-related decline of the Ab and DTH responses occur in parallel, we found different effects of aging on T H and T DTH cells in SAMP1 mice. Furthermore, our data suggest that the reason for the low DTH response in aged SAMP1 mice is not the loss of T DTH cells, but rather the impaired migration of inflammatory cells into the local site.