title: Small intestine CD11c+ CD8+ T cells suppress CD4+ T cell-induced immune colitis.
abstract: The large (LI) and small intestine (SI) differ in patterns of susceptibility to chronic mucosal inflammation. In this study, we evaluated whether this might, in part, reflect differences in resident mucosal CD11c(+) T cells. These cells comprised 39-48% (SI) and 12-17% (LI) of the intraepithelial compartment, most of which were T-cell receptor-αβ(+). In the SI, the majority of these cells were CD103(+) CD8(+) NK1.1(-), whereas the opposite phenotype prevailed in the LI. In transfer models of CD4(+) T cell-induced colitis, small numbers (2.5 × 10(5)) of SI CD11c(+) CD8(+) T cells suppressed proinflammatory cytokine-producing CD4(+) T cells in mesenteric lymph nodes and mucosa-associated lymphoid compartments (SI and LI) and protected mice from chronic inflammation. On a per-cell basis, the regulatory function of SI CD11c(+) T cells in CD4(+) T cell colitis was potent compared with other reported regulatory CD4(+) or CD8(+) T cells. In contrast, neither LI CD11c(+) T cells nor SI CD11c(-) T cells were effective in such immunoregulation. SI CD11c(+) CD8(+) T cells were similarly effective in suppressing CD4(+)CD45RB(hi) T cell colitis, as evidenced by inhibition of intracellular proinflammatory cytokine expression and histological inflammation. These findings indicate that SI CD11c(+) CD8(+) T cells are a distinct intestinal T cell population that plays an immunoregulatory role in control of proinflammatory CD4(+) T cells and maintenance of intestinal mucosal homeostasis.
authors: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California Los Angeles, 90095-1732, USA.
authors: Daisuke
authors: D
authors: Fujiwara
authors: Ling
authors: L
authors: Chen
authors: Bo
authors: B
authors: Wei
authors: Jonathan
authors: J
authors: Braun
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D039521:CD11c Antigen / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D003092:Colitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D004195:Disease Models, Animal; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000172:deficiency / Q000235:genetics; D019672:Genes, T-Cell Receptor; D006706:Homeostasis; D007082:Ileum / Q000276:immunology* / Q000473:pathology; D018928:Immunity, Mucosal; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D007583:Jejunum / Q000276:immunology* / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000235:genetics; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation; D013997:Time Factors
chemical_list: D039521:CD11c Antigen; D016207:Cytokines; D004268:DNA-Binding Proteins; D018836:Inflammation Mediators; C499308:Rag2 protein, mouse; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse; D051960:GTP-Binding Protein alpha Subunit, Gi2; C498016:Gnai2 protein, mouse