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 TCRαβ+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-β 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-β 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 might play a critical role in maintaining mucosal homeostasis during aging.

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