BACKGROUND & AIMS: 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.
BACKGROUND & AIMS: 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: M Camus; S Esses; B Pariente; L Le Bourhis; C Douay; V Chardiny; I Mocan; K Benlagha; E Clave; A Toubert; L Mayer; M Allez Journal: Mucosal Immunol Date: 2013-08-14 Impact factor: 7.313
Authors: Deepa Rana Jamwal; Raji V Marati; Christy A Harrison; Monica T Midura-Kiela; Vanessa R Figliuolo Paz; David G Besselsen; Fayez K Ghishan; Pawel R Kiela Journal: Inflamm Bowel Dis Date: 2020-01-06 Impact factor: 5.325
Authors: B J R Whittle; C Varga; A Berko; K Horvath; A Posa; J P Riley; K A Lundeen; A M Fourie; P J Dunford Journal: Br J Pharmacol Date: 2007-12-24 Impact factor: 8.739