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. Soluble dimeric pMHC class II may be useful in the development of immunospecific therapies for type 1 diabetes.
Casares
Sofia
S
Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA. casars01@doc.mssm.edu
Hurtado
Alicia
A
McEvoy
Robert C
RC
Sarukhan
Adelaida
A
von Boehmer
Harald
H
Brumeanu
Teodor-Doru
TD
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D019281:Dimerization; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010179:Pancreas / Q000276:immunology; D010455:Peptides / Q000276:immunology; D012995:Solubility; D013154:Spleen / Q000276:immunology
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D010455:Peptides