T-cell responses to enteric antigens

Antigens that enter through the intestine induce both local and systemic immune responses by mechanisms that are not well understood. Recent work has established the lamina propria as a immunologically potent compartment, capable of stimulating T cells to antigens delivered from the lumen into the tissue. Several of these studies have characterized the immune potential of lamina propria antigen presenting cell populations, such as macrophages and dendritic cells, as well as the T-cell responses to lumenal infections and parasites. To study the responses of distinct populations of CD4+ T cells to enteric antigens, we have used a T-cell receptor (TCR) transgenic system. First, these studies have shown that intestinal lamina propria T cells represent a unique population of previously activated cells that have been primed in vivo to deliver a wide range of effector functions compared with T cells in the lymphoid tissue. Second, by following activated transgenic T cells with anti-TCR monoclonal antibody, we observed that activation of antigen-specific T cells in the periphery results in the trafficking of distinct subsets to mucosal Peyer's patch and lamina propria compartments. The mechanisms that may explain this trafficking phenomenon are only now becoming clear, with recent work from several laboratories suggesting that a multistep hypothesis, involving the function of various surface selectin and integrin molecules, plays an important role. With these current results, we hypothesize that mucosal and systemic immune responses to oral proteins are determined by the activational state and surface marker phenotype of T-cell subsets that respond. We speculate that a better understanding of these T-cell responses could help develop effective oral vaccination regimens.