Memory/effector (CD45RB(lo)) CD4 T cells are controlled directly by IL-10 and cause IL-22-dependent intestinal pathology

Abstract

The role of direct IL-10 signaling in different T cell subsets is not well understood. To address this, we generated transgenic mice expressing a dominant-negative IL-10 receptor specifically in T cells (CD4dnIL-10Rα). We found that Foxp3-depleted CD45RB(lo) (regulatory T cell [T(reg) cell]-depleted CD45RB(lo)) but not CD45RB(hi) CD4(+) T cells are controlled directly by IL-10 upon transfer into Rag1 knockout (KO) mice. Furthermore, the colitis induced by transfer of T(reg) cell-depleted CD45RB(lo) CD4(+) T cells into Rag1 KO mice was characterized by reduced Th1 and increased Th17 cytokine messenger RNA levels in the colon as compared with the colitis induced by transfer of CD45RB(hi) T cells. In contrast to the CD45RB(hi) transfer colitis model, in which IL-22 is protective, we found that T cell-derived IL-22 was pathogenic upon transfer of T(reg) cell-depleted CD45RB(lo) T cells into Rag1 KO mice. Our results highlight characteristic differences between colitis induced by naive (CD45RB(hi)) and memory/effector (T(reg) cell-depleted CD45RB(lo)) cells and different ways that IL-22 impacts inflammatory bowel disease.