Cooperation of invariant NKT cells and CD4⁺CD25⁺ T regulatory cells in prevention of autoimmune diabetes in non-obese diabetic mice treated with α-galactosylceramide

CD1d-restricted natural killer T (NKT) cells and CD4⁺CD25⁺ regulatory T (Treg) cells are two thymus-derived subsets of regulatory T cells that play an important role in the maintenance of self-tolerance. Yet the functional changes of the two subsets of regulatory T cells in the development of diabetes in non-obese diabetic (NOD) mice remain unclear, and how NKT cells and CD4⁺CD25⁺ Treg cells cooperate functionally in the regulation of autoimmune diabetes is also uncertain. We provide evidence that in NOD mice, an animal model of human type 1 diabetes, the functions of both NKT cells and CD4⁺CD25⁺ Treg cells decrease in an age-dependent manner. We show that treatment with α-galactosylceramide increases the size of the CD4⁺CD25⁺ Treg cell compartment in NOD mice, and augments the expression of forkhead/winged helix transcription factor and the potency of CD4⁺CD25⁺ Treg cells to inhibit proliferation of CD4⁺CD25⁻ T cells. Our data indicate that NKT cells and CD4⁺CD25⁺ Treg cells might cooperate in the prevention of autoimmune diabetes in NOD mice treated with α-galactosylceramide. Induced cooperation of NKT cells and CD4⁺CD25⁺ Treg cells could serve as a strategy to treat human autoimmune disease, such as type 1 diabetes.