The increasing incidence of autoimmune disease in developed societies has been linked with decreased exposure to environmental antigens, implying that antigen exposure modifies immune system development. Vaccination with Group A Streptococci (GAS) produces a strong antibody response to N-acetyl-D-glucosamine (GlcNAc). This GlcNAc moiety is conserved in mammals, and GlcNAcylated proteins are enriched in pancreatic β-cells. Anti-GlcNAc antibodies generated against GAS bind GlcNAc epitopes in human and murine β-cells. Developmental remodeling of the pancreas is accompanied by significant β-cell apoptosis, which may serve as an initial source of autoantigen priming in Type 1 Diabetes (T1D). We therefore hypothesize that anti-GlcNAc IgM generated during GAS infection mediates non-inflammatory clearance of apoptotic β-cell antigens. Using the Min6 insulinoma cells, we demonstrate that β-cell apoptosis results in surface exposure of GlcNAc residues reactive with anti-GAS Abs. During DC priming with irradiated β-cells anti-GlcNAc Abs suppressed CD4 T cell activation and cytokine production. We show that neonatal immunization with GAS, but not Group C Streptococci, reduces the incidence of diabetes in female NOD-mice. Furthermore, passive transfer of anti-GlcNAc Abs protects NOD.Rag1ko mice from diabetes onset following adoptive transfer of diabetogenic BDC2.5 T-cells. Our data suggest that anti-GlcNAc Abs generated by vaccination with GAS can suppress development of T1D.
- Copyright © 2013 by The American Association of Immunologists, Inc.