CD8+CD122+ Regulatory T Cells (Tregs) and CD4+ Tregs Cooperatively Prevent and Cure CD4+ Cell-Induced Colitis

We identified CD8 + CD122 + regulatory T cells (Tregs) and demonstrated their importance in the maintenance of immune homeostasis and in the recovery from experimental autoimmune encephalomyelitis. In this paper, we show that CD8 + CD122 + Tregs effectively prevent and cure colitis in a mouse model. In our experiments, colitis was induced in lymphocyte-deficient RAG-2 −/− mice by transferring CD4 + CD45RB high cells that were excluded with CD4 + Tregs. Cotransfer of CD8 + CD122 + cells clearly suppressed the development of colitis, and this suppressive effect was similar to that of CD4 + CD45RB low cells that were mostly CD4 + Tregs. CD8 + CD122 + cells obtained from IL-10 −/− mice were unable to suppress colitis, indicating that IL-10 is an important effect-transmitting factor in the suppression of colitis. CD8 + CD122 + cells showed a suppressive effect when they were transferred 4 wk after CD4 + CD45RB high cells, indicating the therapeutic potential of CD8 + CD122 + cells. A mixture of CD8 + CD122 + cells and CD4 + CD45RB low cells was far more effective than single Tregs, indicating the synergistic effect of these Tregs. These overall findings demonstrate the potential role of CD8 + Tregs, and possibly together with CD4 + Tregs, in the medical care of inflammatory bowel disease patients.