CD4+CD25+ cell depletion from the normal CD4+ T cell pool prevents tolerance toward the intestinal flora and leads to chronic colitis in immunodeficient mice

Background: CD4(+)CD25(+) regulatory T cells have been shown to prevent immune-mediated colitis in mice; however, it is unclear whether the absence of CD4(+)CD25(+) in the normal CD4(+) T cell pool is responsible for the development of chronic colitis. Using the T cell-deficient Tg is an element of 26 mouse model, we show that CD4(+)CD25(-) cells but not CD4(+)CD25(+) cells induce a severe intestinal inflammation. Transfer of CD4(+)CD25(+) cells, together with CD4(+)CD25(-) cells, ameliorated intestinal inflammation, and reconstitution with the whole mesenteric lymph node cell pool did not induce colitis in recipients. Transferred CD4(+)CD25(-) cells were found mainly in the mesenteric lymph nodes, where they showed an activated T(H)l-like phenotype. In the absence of regulatory CD4(+)CD25(+) T cells, recipient CD4(+). cells secreted IFN-gamma in response to stimulation with intestinal bacterial antiqen that was prevented in vivo and in vitro by regulatory CD4(+)CD25(-) cells. These studies suggest that CD4(+)CD25(-) cells have a strong, colitogenic effect in the Tg is an element of 26 colitis model and that CD4(+)CD25(-) cells may be the main regulators that prevent or downregulate the proinflammatory effect of colitolenic T cells in the Tg is an element of 26 mouse model.