IL-6 positively regulates Foxp3+CD8+ T cells in vivo.

Although recent studies have identified regulatory roles for Foxp3(+)CD8(+) T cells, the mechanisms that induce their development and underlie their functions in vivo have not been elucidated. Here, we show that IL-6 positively regulates the Foxp3(+)CD8(+) T-cell development and function. The Foxp3(+)CD8(+) T cells that differentiated in vitro in the presence of IL-6 suppressed autoimmune colitis and arthritis in vivo. Moreover, Foxp3(+)CD8(+) T cells that developed in vivo in the presence of enhanced IL-6 signaling suppressed the development of a spontaneous T(h)17 cell-mediated autoimmune arthritis. Thus, we concluded that Foxp3(+)CD8(+) T cells develop in response to IL-6 and regulate chronic inflammation in T(h)17 cell-mediated F759 autoimmune arthritis. These results suggested that Foxp3(+)CD8(+) T cells may develop in response to IL-6 under certain inflammatory conditions in vivo and may regulate some other chronic inflammation diseases.