In vivo enhancement of dendritic cell function

Abstract

Despite the apparent positive recognition of antigen by mucosal T cells after ingesting food, the default functional response in the gut is tolerance. Although dendritic cells (DCs) are classically defined as potent stimulatory antigen-presenting cells, we have previously shown that tolerance is enhanced in vivo in the presence of elevated numbers of DCs. In order to more closely investigate the mechanistic basis of tolerance induction, we have focused our subsequent studies on identifying features peculiar to mucosal dendritic cells and the functional involvement of mucosal DCs in driving the early T cell response to fed antigen. These studies have revealed a population of DCs in the mucosae that exhibit the plasmacytoid phenotype and secrete IFN-alpha following stimulation with CpG, and can drive differentiation of naive T cells into cells that exhibit regulatory properties. The activity of these DCs also failed to sustain robust T cell proliferation and, rather, functioned to enhance the suppressive efficacy of CD4(+)CD25(+) T regulatory cells. Given their significant presence in mucosal tissue, these DCs likely provide a mechanistic basis for the homeostatic regulation prominent in the gut, presumably by eliciting regulatory cell suppressor function and poorly supporting T helper cell proliferation. These studies further underscore the critical role for intestinal DCs in promoting tolerogenic antigen presentation at a site of high antigenic stimulation.