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.