γδ T cells support gut Ag-reactive colitogenic effector T-cell generation by enhancing Ag presentation by CD11b+ DCs in the mesenteric LN

Abstract

Abstract T cells expressing the γδ TCR are dominant T-cell subsets in the intestinal immune system. We previously demonstrated that γδ T cells play important roles in augmenting Th17-type colitogenic immune responses in a T cell-induced colitic inflammation model. However, its underlying mechanism remains poorly understood. In this study, an in vitro coculture system using effector T cells enriched in gut Ag-reactive cells was employed as a readout tool to search for gut Ag presenting APCs. We found that the presence of γδ T cells dramatically enhances gut Ag presentation within the mLN in mice. Mesenteric MHCII+ CD11c+ DCs from TCRβ−/− induce massive proliferation of colitogenic T cells but not DCs from γδ T cells deficient mice. Gut Ag presentation by CD11b+ DC subsets was particularly controlled by γδ T cells. Interestingly, γδ T cell entry to the lymph nodes was essential to improve the Ag presentation. Therefore, our results highlight that γδ T cells play a previously unrecognized role to support colitogenic immunity by regulating gut Ag presentation in the draining LN.