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

• DOI: 10.1084/jem.20021345
• Publication Date: 2003-01-06T19:02:37Z
• Authors: Kevin J. Maloy; Laurence Salaun; Rachel Cahill; Gordon Dougan; Nigel J. Saunders; Fiona Powrie
• Keywords: T-Lymphocytes; 610; Article; Helicobacter Infections; Mice; 03 medical and health sciences; 0302 clinical medicine; Mucosal immunity; Transforming Growth Factor beta; Helicobacter; 616; Animals; Inflammation; Immune tolerance; Receptors, Interleukin-2; Regulatory T cells; Adoptive Transfer; Immunity, Innate; Interleukin-10; 3. Good health; Intestines; IL-10; CD4 Antigens; Cytokines

CD4+CD25+ regulatory T (TR) 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+ TR 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+ TR cells. T cell–independent pathology was accompanied by activation of the innate immune system that was also inhibited by CD4+CD25+ TR 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+ TR cells do not only suppress adaptive T cell responses, but are also able to control pathology mediated by innate immune mechanisms.