CD4+CD25+ TR cells suppress innate immune pathology through cytokine-dependent mechanisms

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 beta. 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.