Down-regulation of diabetogenic CD4⁺ T cells by a soluble dimeric peptide-MHC class II chimera

Type I diabetes is an organ-specific autoimmune disease that is mediated by autoreactive T cells. We show here that administration of a soluble dimeric peptide-major histocompatibility complex (pMHC) class II chimera (DEF) to prediabetic double-transgenic mice prevents the onset of disease or, in animals that are already diabetic, restores normoglycemia. The antidiabetogenic effects of DEF rely on the induction of anergy in splenic autoreactive CD4⁺ T cells via alteration of early T cell receptor signaling and stimulation of interleukin 10-secreting T regulatory type I cells in the pancreas. Soluble dimeric pMHC class II may be useful in the development of immunospecific therapies for type I diabetes.