Control of intestinal inflammation by regulatory T cells

Transfer of CD4(+) T cells to immune-deficient mice in the absence of the C D25(+) subset leads to the development of colitis, indicating that regulato ry cells capable of controlling a bacteria-driven inflammatory response are present in normal mice. Cells with this function are present in the thymus as well as in the periphery of germ-free mice, suggesting they may be reac tive with self-antigen. These cells resemble CD4(+)CD25(+) cells that inhib it organ-specific autoimmunity suggesting that a similar subset of regulato ry T cells may control responses to self and foreign antigens. Development of colitis is dependent on accumulation of activated CD134L(+) dendritic ce lls (DC) in the mesenteric lymph nodes, which is inhibited by CD4(+)CD25(+) cells, indicating that regulatory T cells may control DC activation in viv o. Whilst inhibition of T-cell activation in vitro by CD4(+)CD25(+) cells d oes not involve interleukin-10 and transforming growth factor-beta, these c ytokines are required for the suppression of colitis. It may be that contro l of responses that activate the innate immune system requires multiple mec hanisms of immune suppression. Recently, we identified CD4(+)CD25(+) cells with immune suppressive activity in the thymus and peripheral blood of huma ns, raising the possibility that dysfunction in thin, mechanism of immune r egulation may be involved in the development of autoimmune and inflammatory diseases.