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Circulatory antigen processing by mucosal dendritic cells controls CD8(+) T cell activation

Chang, SY;Song, JH;Guleng, B;Cotoner, CA;Arihiro, S;Zhao, Y;Chiang, HS;O'Keeffe, M;Liao, G;Karp, CL;Kweon, MN;Sharpe, AH;Bhan, A;Terhorst, C;Reinecker, HC;

Circulatory antigens transit through the small intestine via the fenestrated capillaries in the lamina propria prior to entering into the draining lymphatics. But whether or how this process controls mucosal immune responses remains unknown. Here we demonstrate that dendritic cells (DCs) of the lamina propria can sample and process both circulatory and luminal antigens. Surprisingly, antigen cross-presentation by resident CX3CR1(+) DCs induced differentiation of precursor cells into CD8(+) T cells that expressed interleukin-10 (IL-10), IL-13, and IL-9 and could migrate into adjacent compartments. We conclude that lamina propria CX3CR1(+) DCs facilitate the surveillance of circulatory antigens and act as a conduit for the processing of self- and intestinally absorbed antigens, leading to the induction of CD8(+) T cells, that partake in the control of T cell activation during mucosal immune responses.