CD4+CD25+ regulatory T cells selectively diminish systemic autoreactivity in arthritic K/BxN mice

Although the arthritis symptoms observed in the K/BxN model have been shown to be dependent on the functions of T and B cells specific to the self antigen glucose-6-phosphate isomerase, less is known about the in vivo roles of CD4(+)CD25(+) regulatory T (T(reg)) cells in the pathology of K/BxN mice. We determined the quantitative and functional characteristics of the T(reg) cells in K/BxN mice. These mice contained a higher percentage of Foxp3(+) T(reg) cells among the CD4(+) T cells than their BxN littermates. These T(reg) cells were anergic and efficiently suppressed the proliferation of naïve CD4(+) T cells and cytokine production by effector CD4(+) T cells in vitro. Antibody-mediated depletion of CD25(+) cells caused K/BxN mice to develop multi-organ inflammation and autoantibody production, while the symptoms of arthritis were not affected. These results demonstrate that despite the inability of the T(reg) cells to suppress arthritis development, they play a critical role protecting the arthritic mice from systemic expansion of autoimmunity.