An Essential Role for Interleukin 10 in the Function of Regulatory T Cells That Inhibit Intestinal Inflammation

Abstract

A T helper cell type 1–mediated colitis develops in severe combined immunodeficient mice after transfer of CD45RB ^high CD4 ⁺ T cells and can be prevented by cotransfer of the CD45RB ^low subset. The immune-suppressive activities of the CD45RB ^low T cell population can be reversed in vivo by administration of an anti-transforming growth factor β antibody. Here we show that interleukin (IL)-10 is an essential mediator of the regulatory functions of the CD45RB ^low population. This population isolated from IL-10–deficient (IL-10 ^−/−) mice was unable to protect from colitis and when transferred alone to immune-deficient recipients induced colitis. Treatment with an anti–murine IL-10 receptor monoclonal antibody abrogated inhibition of colitis mediated by wild-type (WT) CD45RB ^low CD4 ⁺ cells, suggesting that IL-10 was necessary for the effector function of the regulatory T cell population. Inhibition of colitis by WT regulatory T cells was not dependent on IL-10 production by progeny of the CD45RB ^high CD4 ⁺ cells, as CD45RB ^low CD4 ⁺ cells from WT mice were able to inhibit colitis induced by IL-10 ^−/− CD45RB ^high CD4 ⁺ cells. These findings provide the first clear evidence that IL-10 plays a nonredundant role in the functioning of regulatory T cells that control inflammatory responses towards intestinal antigens.