title: CD8+ cytotoxic T cells induce relapsing colitis in normal mice.
abstract: OBJECTIVE
  Most mouse models of IBD have emphasized an effector role of type-1 CD4+ T cells in colitis. The aim of this study was to develop a model of antigen-specific relapsing colitis to investigate the relative contribution of CD4+ and CD8+ effectors.
  
  
  METHODS
  Balb/C mice were sensitized and challenged with a suboptimal dose of 2.4 dinitrobenzene sulfonic acid to generate a colonic delayed-type hypersensitivity response. The respective role of CD4+ and CD8+ T cells in the initiation of colitis was analyzed by in vivo monoclonal antibody depletion and cell-transfer experiments. Dynamic and function of the colitogenic effectors were studied by immunohistochemistry, fluorescence-activated cell sorter analysis, enzyme-linked immunospot assay, quantitative polymerase chain reaction, and in vivo CTL assays.
  
  
  RESULTS
  Relapsing colitis rapidly occurred only after challenge of previously sensitized mice. Interferon-gamma-producing cytotoxic CD8+ T cells (Tc1) specific for hapten-modified self-proteins were generated in colon-draining lymph nodes on day 5 after sensitization, before the onset of disease. These CD8+ T cells were rapidly recruited upon challenge into colon lamina propria as granzyme B-expressing effectors exerting ex vivo cytotoxicity against syngeneic hapten-modified colonic epithelial cells. Colitis was prevented by in vivo antibody depletion of CD8+, but not of CD4+, T cells and could be induced in naive recipients within 48 hours after transfer of CD8+, but not CD4+, T cells purified from sensitized mice.
  
  
  CONCLUSIONS
  Our data show that antigen-specific CD8+ T cells can induce relapsing colitis in normal mice and suggest that the cytolytic function of CD8 Tc1 against epithelial cells may initiate the intestinal inflammatory process.
authors.affiliation: INSERM U 404 Immunité et Vaccination, CERVI, IFR 128 Biosciences Lyon-Gerland, Lyon, F-69007, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Nancey
authors.forename: Sébastien
authors.initials: S
authors.lastname: Holvöet
authors.forename: Ivan
authors.initials: I
authors.lastname: Graber
authors.forename: Grégoire
authors.initials: G
authors.lastname: Joubert
authors.forename: David
authors.initials: D
authors.lastname: Philippe
authors.forename: Stefan
authors.initials: S
authors.lastname: Martin
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Nicolas
authors.forename: Pierre
authors.initials: P
authors.lastname: Desreumaux
authors.forename: Bernard
authors.initials: B
authors.lastname: Flourié
authors.forename: Dominique
authors.initials: D
authors.lastname: Kaiserlian
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003092:Colitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D012008:Recurrence; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D004247:DNA