These same expanded BDC-2.5 Tregs were also capable of attenuating spontaneous diabetes in the following diabetes models: NOD.CD28-/- mice (285), NOD.scid mice that were treated with splenocytes from diabetic NOD mice (286), or spontaneous diabetes in wild-type, pre-diabetic (13 weeks age) NOD mice (287). Here, CD28 is linked to diabetes mellitus.