Functional specialization of gut CD103+ dendritic cells in the regulation of tissue-selective T cell homing

Gut-associated lymphoid tissue (GALT) dendritic cells (DCs) display a unique ability to generate CCR9(+) alpha(4)beta(+)(7) gut-tropic CD8(+) effector T cells. We demonstrate efficient induction of CCR9 and alpha(4)beta(7) on CD8(+) T cells in mesenteric lymph nodes (MLNs) after oral but not intraperitoneal (i.p.) antigen administration indicating differential targeting of DCs via the oral route. In vitro, lamina propria (LP)-derived DCs were more potent than MLN or Peyer's patch DCs in their ability to generate CCR9(+)alpha(4)beta(+)(7) CD8(+) T cells. The integrin alpha chain CD103 (alpha(E)) was expressed on almost all LP DCs, a subset of MLN DCs, but on few splenic DCs. CD103(+) MLN DCs were reduced in number in CCR7(-/-) mice and, although CD8(+) T cells proliferated in the MLNs of CCR7(-/-) mice after i.p. but not oral antigen administration, they failed to express CCR9 and had reduced levels of alpha(4)beta(7). Strikingly, although CD103(+) and CD103(-) MLN DCs were equally potent at inducing CD8(+) T cell proliferation and IFN-gamma production, only CD103(+) DCs were capable of generating gut-tropic CD8(+) effector T cells in vitro. Collectively, these results demonstrate a unique function for LP-derived CD103(+) MLN DCs in the generation of gut-tropic effector T cells.