B7/CD28 costimulation is essential for the homeostasis of the CD4(+)CD25(+) immunoregulatory T cells that control autoimmune diabetes

CD28/B7 costimulation has been implicated in the induction and progression of autoimmune diseases. Experimentally induced models of autoimmunity have been shown to be prevented or reduced in intensity in mice rendered deficie nt for CD28 costimulation. In sharp contrast, spontaneous diabetes is exace rbated in both B7-1/B7-2-deficient and CD28-deficient NOD mice. These mice present a profound decrease of the immunoregulatory CD4(+)CD25(+) T cells, which control diabetes in prediabetic NOD mice. These cells are absent from both CD28KO and B7-1/B7-2KO mice, and the transfer of this regulatory T ce ll subset from control NOD animals into CD28-deficient animals can delay/pr event diabetes. The results suggest that the CD28/B7 costimulatory pathway is essential for the development and homeostasis of regulatory T cells that control spontaneous autoimmune diseases.