Effect of ingested interferon-alpha on beta-cell function in children with new-onset type 1 diabetes.

Objective: To evaluate the safety and efficacy of ingested human recombinant interferon-alpha (hrIFN-alpha) for preservation of beta-cell function in young patients with recent-onset type 1 diabetes.

Research Design And Methods: Subjects aged 3-25 years in whom type 1 diabetes was diagnosed within 6 weeks of enrollment were randomly assigned to receive ingested hrIFN-alpha at 5,000 or 30,000 units or placebo once daily for 1 year. The primary outcome was change in C-peptide secretion after a mixed meal.

Soluble, dimeric HLA DR4-peptide chimeras: an approach for detection and immunoregulation of human type-1 diabetes.

Still there are no effective methods to predict or cure type 1 diabetes (T1D) in humans. Soluble, dimeric MHC class II-peptide (DEF) chimeras have potential for both early diagnosis and immunospecific therapy. DEF chimeras prevent and reverse diabetes in mice by stimulating antigen-specific type 1 T regulatory cell (Tr1)-like cells.

Immunokinetics of autoreactive CD4 T cells in blood: a reporter for the "hit-and-run" autoimmune attack on pancreas and diabetes progression.

Little is known about the fate of autoreactive CD4 T cells in blood. Using a mouse model for spontaneous autoimmune diabetes we demonstrated that the status of the autoimmune process in pancreas could be pictured through the frequency and phenotype of autoreactive CD4 T cells in the blood. Early during the prediabetic stage, the frequency of these cells in blood decreased as a consequence of their recruitment in the pancreas.

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

Type 1 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 1 cells in the pancreas.