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.

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.

Relapsing colitis rapidly occurred only after challenge of previously sensitized mice. Interferon-γ–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.

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.