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

Nat Med. 2003 Feb;9(2):198-205. doi: 10.1038/nm818. Epub 2003 Jan 21.


Pancreatic islets of Langerhans are enveloped by peri-islet Schwann cells (pSC), which express glial fibrillary acidic protein (GFAP) and S100beta. 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 beta-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 S100beta 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 beta-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoantibodies / analysis
  • Autoantibodies / immunology
  • Base Sequence
  • DNA Primers
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Fluorescent Antibody Technique
  • Glial Fibrillary Acidic Protein / metabolism
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / pathology
  • Male
  • Mice
  • Mice, Inbred Strains
  • Nerve Growth Factors / metabolism
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins / metabolism
  • Schwann Cells / immunology
  • Schwann Cells / metabolism
  • Species Specificity


  • Autoantibodies
  • DNA Primers
  • Glial Fibrillary Acidic Protein
  • Nerve Growth Factors
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins