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 alpha4beta7 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+alpha4beta7+CD62Llow, 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.
Johansson-Lindbom
Bengt
B
Immunology Section, Dept. of Cell and Molecular Biology, Lund University, BMC I-13, S-22184 Lund, Sweden. Bengt.Johansson_Lindbom@immuno.lu.se
Svensson
Marcus
M
Wurbel
Marc-André
MA
Malissen
Bernard
B
Márquez
Gabriel
G
Agace
William
W
D000276:Adjuvants, Immunologic / Q000378:metabolism*; D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D039441:Integrin alpha4 / Q000378:metabolism; D039641:Integrin beta Chains / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D019041:L-Selectin / Q000378:metabolism; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054388:Receptors, CCR; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; C119309:CC chemokine receptor 9; D039641:Integrin beta Chains; D054388:Receptors, CCR; D019707:Receptors, Chemokine; C091368:integrin beta7; D019041:L-Selectin; D039441:Integrin alpha4