Journal Article

Autoimmune islet destruction in spontaneous type 1 diabetes is not β-cell exclusive

Li, Xiaomao, Sampson, Anastazia, Tsui, Hubert, Santamaria, Pere, Jackowski, George, Afifiyan, Fatemeh, Becker, Dorothy J., Song, Aihua, Winer, Shawn, Ohashi, Pamela, Dosch, H -Michael, Lau, Ambrose, Cheung, Roy K., Elford, Alisha

2003

Overview

Pancreatic islets of Langerhans are enveloped by peri-islet Schwann cells (pSC), which express glial fibrillary acidic protein (GFAP) and S100β. pSC-autoreactive T- and B-cell responses arise in 3- to 4-week-old diabetes-prone non-obese diabetic (NOD) mice, followed by progressive pSC destruction before detectable β-cell death. Humans with probable prediabetes generate similar autoreactivities, and autoantibodies in islet-cell autoantibody (lCA) –positive sera co-localize to pSC. Moreover, GFAP-specific NOD T-cell lines transferred pathogenic peri-insulitis to NOD/severe combined immunodeficient (NOD/SCID) mice, and immunotherapy with GFAP or S100β prevented diabetes. pSC survived in rat insulin promoter Iymphocytic choriomeningitis virus (rip–LCMV) glycoprotein/CD8 + T-cell receptor gp double-transgenic mice with virus-induced diabetes, suggesting that pSC death is not an obligate consequence of local inflammation and β-cell destruction. However, pSC were deleted in spontaneously diabetic NOD mice carrying the CD8 + /8.3 T-cell receptor transgene, a T cell receptor commonly expressed in earliest islet infiltrates. Autoimmune targeting of pancreatic nervous system tissue elements seems to be an integral, early part of natural type 1 diabetes.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Animals / Autoantibodies - analysis / Autoantibodies - immunology / Base Sequence / Biomedical and Life Sciences / Biomedicine / Cancer Research / Diabetes Mellitus, Type 1 - immunology / DNA Primers / Female / Fluorescent Antibody Technique / Glial Fibrillary Acidic Protein - metabolism / Infectious Diseases / Islets of Langerhans - immunology / Islets of Langerhans - pathology / Male / Metabolic Diseases / Mice / Mice, Inbred Strains / Molecular Medicine / Nerve Growth Factors - metabolism / Neurosciences / S100 Calcium Binding Protein beta Subunit / S100 Proteins - metabolism / Schwann Cells - immunology / Schwann Cells - metabolism / Species Specificity