In order to exclude the effect of non-T-cell derived IL-22, which has been recently reported to have a protective function in CRC6 and also to exclude effects of TGF-β on CD8+ T cells, we repopulated Il22-deficient lymphopenic hosts (Rag1−/−Il22−/−) with either wild type (WT), TGF-β-DNR transgenic (Tg), Il22−/− or TGF-β-DNR transgenic × Il22−/− (Tg × Il22−/−) CD4+ T cells and induced colitis-associated colon cancer upon engraftment using the AOM/DSS model. The gene discussed is IL22; the disease is colitis.