CD4+CD25− T cells induce severe colitis when injected into immunodeficient recipients. The migration of disease-inducing cells to the bowel is controlled by adhesion molecules and chemotactic proteins. Chemokine receptors expressed on the T cells are therefore potential targets for anti-inflammatory therapy in inflammatory bowel disease. In this study, we have investigated the role of the chemokine receptor CXCR3 in the development of chronic colitis in a murine model.Method
Expression of CXCR3 on CD4+ T cell from normal and colitic mice was assessed by flow cytometry. Development of colitis was followed after transfer of either normal or CXCR3−CD4+CD25−T cell into immunodeficient host. In addition, the ability of regulatory T cell to function in vivo in the absence of CXCR3 was tested.Results
We find CXCR3 to be expressed on 80% to 90% of CD4+ T cells isolated from colitic mice compared with only 4% to 10% of CD4+ T cells in normal naïve mice. Injecting CD4+CXCR3−CD25− T cells into immunodeficient hosts results in an ameliorated form of colitis with a lack of clinical symptoms, suggesting that CXCR3 expression is important for enteroantigen priming of CD4+ T cells and/or subsequent migration into the gut wall. In contrast, CXCR3 expression does not affect the function of regulatory T cells because CXCR3−/− regulatory T cells are just as capable as their wild-type counterpart of controlling disease development. The diminished disease-inducing capability of CXCR3−/− T cells is not caused by the absence of enteroantigen specificity; we also tested the enteroantigen-specific proliferative ability of CD4+CD25− T cells from CXCR3−/− mice in vitro and found that they respond even more strongly than wild-type cells.Conclusions
The present data indicate that CXCR3 plays an important role in controlling the migration of disease-inducing CD4+CD25− T cells into the gut wall. In contrast, lack of CXCR3 expression by regulatory T cells does not compromise their function in this model of colitis.