Selective generation of gut tropic T cells in gut-associated lymphoid tissue (GALT):: Requirement for GALT dendritic cells and adjuvant

In the current study, we address the underlying mechanism for the selective generation of gut-homing T cells in the gut-associated lymphoid tissues (GALT). We demonstrate that DCs in the GALT are unique in their capacity to establish T cell gut tropism but in vivo only confer this property to T cells in the presence of DC maturational stimuli, including toll-like receptor-dependent and -independent adjuvants. Thus, DCs from mesenteric LNs (MLNs), but not from spleen, supported expression of the chemokine receptor CCR9 and integrin alpha(4)beta(7) by activated CD8(+) T cells. While DCs were also required for an efficient down-regulation of CD62L, this function was not restricted to MLN DCs. In an adoptive CD8(+) T cell transfer model, antigen-specific T cells entering the small intestinal epithelium were homogeneously CCR9(+)alpha(4)beta(7)(+)CD62L(low), and this phenotype was only generated in GALT and in the presence of adjuvant. Consistent with the CCR9(+) phenotype of the gut-homing T cells, CCR9 was found to play a critical role in the localization of T cells to the small intestinal epithelium. Together, these results demonstrate that GALT DCs and T cell expression of CCR9 play critical and integrated roles during T cell homing to the gut.