Fas and Fas ligand expression in inflamed islets in pancreas sections of patients with recent-onset Type I diabetes mellitus

Diabetologia. 1999 Nov;42(11):1332-40. doi: 10.1007/s001250051446.


Aims/hypothesis: 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.

Conclusion/interpretation: 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]

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Diabetes Mellitus, Type 1 / metabolism*
  • Diabetes Mellitus, Type 1 / pathology
  • Fas Ligand Protein
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Inflammation / metabolism
  • Inflammation / pathology
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / pathology
  • Islets of Langerhans / physiopathology
  • Male
  • Membrane Glycoproteins / metabolism*
  • Middle Aged
  • Pancreas / metabolism
  • Phenotype
  • fas Receptor / metabolism*


  • FASLG protein, human
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • fas Receptor