title: Fas and Fas ligand expression in inflamed islets in pancreas sections of patients with recent-onset Type I diabetes mellitus.
abstract: OBJECTIVE
  Type I (insulin-dependent) diabetes results mainly from T-cell-mediated autoimmune destruction of pancreatic beta cells. Cytotoxic T lymphocytes destroy target cells via a perforin-based or Fas-based mechanism. Our previous study indicated that the Fas-Fas ligand (FasL) pathway is required for the development of autoimmune diabetes in the NOD mouse. We now investigated whether or not the Fas-FasL system is involved in the beta-cell destruction in human Type I diabetes.
  
  
  METHODS
  We immunohistochemically analysed pancreas biopsy specimens of 13 recent-onset patients.
  
  
  RESULTS
  Pancreatic islets were identified but showed various degrees of reduction in beta-cell volume in all patients. Out of 13 patients 6 had insulitis. In these 6 patients Fas was expressed in both the islets and infiltrating cells but not in either cell type in the 7 other patients without insulitis. Double immunostaining showed that Fas was positive in 92.2 to 97.7 % of beta cells but only in 17.6 to 46.7 % of alpha cells in Fas-positive, insulin-remaining islets. We found FasL was expressed exclusively in islet-infiltrating cells in patients with insulitis. Double immunostaining revealed that the most prevalent phenotype of FasL-positive cells was CD8, which was followed by macrophages and CD4.
  
  
  CONCLUSIONS
  The interaction between Fas on beta cells and FasL on infiltrating cells might trigger selective apoptotic beta-cell death in inflamed islets, leading to immune-mediated Type I diabetes. [Diabetologia (1999) 42: 1332-1340]
authors.affiliation: Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Moriwaki
authors.forename: N
authors.initials: N
authors.lastname: Itoh
authors.forename: J
authors.initials: J
authors.lastname: Miyagawa
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: A
authors.initials: A
authors.lastname: Imagawa
authors.forename: K
authors.initials: K
authors.lastname: Yamagata
authors.forename: H
authors.initials: H
authors.lastname: Iwahashi
authors.forename: H
authors.initials: H
authors.lastname: Nakajima
authors.forename: M
authors.initials: M
authors.lastname: Namba
authors.forename: S
authors.initials: S
authors.lastname: Nagata
authors.forename: T
authors.initials: T
authors.lastname: Hanafusa
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D000293:Adolescent; D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000473:pathology; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism; D010641:Phenotype; D019014:fas Receptor / Q000378:metabolism*
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor