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

Abstract

Gut-associated lymphoid tissue (GALT) dendritic cells (DCs) display a unique ability to generate CCR9 ⁺ α ₄ β ₇ ⁺ gut-tropic CD8 ⁺ effector T cells. We demonstrate efficient induction of CCR9 and α ₄ β 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 ⁺ α ₄ β ₇ ⁺ CD8 ⁺ T cells. The integrin α chain CD103 ( α _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 α ₄ β ₇. Strikingly, although CD103 ⁺ and CD103 ⁻ MLN DCs were equally potent at inducing CD8 ⁺ T cell proliferation and IFN- γ 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.