Cure of innate intestinal immune pathology by CD4+CD25+ regulatory T cells

CD4+CD25+ regulatory T (TR) cells are a naturally occurring population of T cells that suppress the development of a variety of pathological immune responses. However, as human inflammatory diseases are usually not diagnosed until after the onset of clinical symptoms, it is of great interest to determine whether CD4+CD25+ TR cells can reverse established pathology. To examine this question we have utilized a murine model of human inflammatory bowel disease (IBD), where pathology is triggered by infection of immune deficient RAG−/− mice with the pathogenic bacterium Helicobacter hepaticus. Here we demonstrate that adoptively transferred CD4+CD25+ TR cells can cure established intestinal inflammation that is mediated by innate immune activation in H. hepaticus-infected RAG−/− mice. CD4+CD25+ TR cell-mediated amelioration of innate intestinal pathology was accompanied by a reversal in systemic innate immune activation, but did not involve any detectable anti-bacterial effects, as bacterial colonization levels were unchanged. Cure of established pathology was not achieved using subpopulations of CD4+CD25− T cells, further emphasizing the enhanced regulatory activity of CD4+CD25+ TR cells.