ABSTRACT
Aging is reported to be associated with decline in oral tolerance induction, which is initiated at the intestinal mucosal surface. Herein, we examined the effect of aging in T cells and cytokines at the intestinal mucosa that might be involved in oral tolerance induction. Frequencies of regulatory-type IEL subsets such as TCRγδ(+) and TCRαß(+)CD8αα(+) were lower in aged mice. Mucosal CD4(+)CD25(+)Foxp3(+) and CD4(+)LAP(+) T cells increased with aging but activated CD44(+)CD4(+) mucosal T cells also augmented. Production of TGF-ß and IL-10 in the small intestine of old mice was reduced. Moreover, the ability of mucosal dendritic cells of aged mice to stimulate TGF-ß secretion and differentiation of CD4(+)LAP(+) T cells in co-culture studies also declined with aging. Reduction in these regulatory-type cytokines and T cells may help to explain the decline in susceptibility to oral induction during aging. However, not all mucosal regulatory elements were altered by aging and CD4(+)CD25(+)Foxp3(+) T cells were especially resistant to changes. Persistence of some mechanisms of regulation may play a critical role in maintaining mucosal homeostasis during aging.
