Cure of innate intestinal immune pathology by CD4+CD25+ regulatory T cells.
CD4+CD25+ regulatory T (T(R)) 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+ T(R) 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+ T(R) cells can cure established intestinal inflammation that is mediated by innate immune activation in H. hepaticus-infected RAG-/- mice. CD4+CD25+ T(R) 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+ T(R) cells.
Maloy
Kevin J
KJ
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK. kevin.maloy@path.ox.ac.uk
Antonelli
Lis R V
LR
Lefevre
Marie
M
Powrie
Fiona
F
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D007422:Intestines / Q000276:immunology* / Q000473:pathology*; D015375:Receptors, Interleukin-2 / Q000276:immunology*
D015375:Receptors, Interleukin-2