title: 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+alpha4beta7+ gut-tropic CD8+ effector T cells. We demonstrate efficient induction of CCR9 and alpha4beta7 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+alpha4beta7+ CD8+ T cells. The integrin alpha chain CD103 (alphaE) 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 alpha4beta7. 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.
authors.affiliation: Immunology Section, Lund University, BMC I-13, 221 84 Lund, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Johansson-Lindbom
authors.forename: Marcus
authors.initials: M
authors.lastname: Svensson
authors.forename: Oliver
authors.initials: O
authors.lastname: Pabst
authors.forename: Caroline
authors.initials: C
authors.lastname: Palmqvist
authors.forename: Gabriel
authors.initials: G
authors.lastname: Marquez
authors.forename: Reinhold
authors.initials: R
authors.lastname: Förster
authors.forename: William W
authors.initials: WW
authors.lastname: Agace
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D039001:Integrin alpha Chains / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054388:Receptors, CCR; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology
chemical_list: D015703:Antigens, CD; C119309:CC chemokine receptor 9; C515371:Ccr7 protein, mouse; D039001:Integrin alpha Chains; D054388:Receptors, CCR; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; C091367:alpha E integrins; D007371:Interferon-gamma