Mice that have a truncated mutation of the common cytokine receptor γ chain (CRγ^−/Y) are known to spontaneously develop colitis. To identify the pathologic elements responsible for triggering this localized inflammatory disease, we elucidated and characterized aberrant T cells and their enteropathogenic cytokines in CRγ^−/Y mice with colitis.

The histologic appearance, cell population, T-cell receptor Vβ usage, and cytokine production of lamina propria lymphocytes were assessed. CRγ^−/Y mice were treated with anti-interleukin (IL)-6 receptor monoclonal antibody to evaluate its ability to control colitis, and splenic CD4⁺ T cells from the same mouse model were adoptively transferred into SCID mice to see if they spurred the appearance of colitis.

We found marked thickening of the large intestine, an increase in crypt depth, and infiltration of the colonic lamina propria and submucosa with mononuclear cells in the euthymic CRγ^−/Y mice, but not in the athymic CRγ^−/Y mice, starting at the age of 8 weeks. Colonic CD4⁺ T cells with high expressions of antiapoptotic Bcl-x and Bcl-2 were found to use selected subsets (Vβ14) of T-cell receptor and to exclusively produce IL-6. Treatment of CRγ^−/Y mice with anti-IL-6 receptor monoclonal antibody prevented the formation of colitis via the induction of apoptosis in IL-6-producing CD4⁺ T cells. Adoptive transfer of pathologic CD4⁺ T cells induced colitis in the recipient SCID mice.

Colonic IL-6-producing thymus-derived CD4⁺ T cells are responsible for the development of colitis in CRγ^−/Y mice.