CD4+CD25+ TR Cells Suppress Innate Immune Pathology Through Cytokine-dependent Mechanisms

Abstract

CD4⁺CD25⁺ regulatory T (T_R) cells can inhibit a variety of autoimmune and inflammatory diseases, but the precise mechanisms by which they suppress immune responses in vivo remain unresolved. Here, we have used Helicobacter hepaticus infection of T cell–reconstituted recombination-activating gene (RAG)^−/− mice as a model to study the ability of CD4⁺CD25⁺ T_R cells to inhibit bacterially triggered intestinal inflammation. H. hepaticus infection elicited both T cell-mediated and T cell–independent intestinal inflammation, both of which were inhibited by adoptively transferred CD4⁺CD25⁺ T_R cells. T cell–independent pathology was accompanied by activation of the innate immune system that was also inhibited by CD4⁺CD25⁺ T_R cells. Suppression of innate immune pathology was dependent on T cell–derived interleukin 10 and also on the production of transforming growth factor β. Thus, CD4⁺CD25⁺ T_R cells do not only suppress adaptive T cell responses, but are also able to control pathology mediated by innate immune mechanisms.