A possible involvement of Fas-Fas ligand signaling in the pathogenesis of murine autoimmune gastritis

Gastroenterology. 1996 Oct;111(4):959-67. doi: 10.1016/s0016-5085(96)70063-x.


Background & aims: A Th1 clone, II-6, established from an autoimmune gastritis BALB/c mouse that underwent thymectomy 3 days after birth, recognized a 15 mer peptide constructing the alpha subunit of H+, K(+)-adenosine triphosphatase as antigen and induced gastritis in nu/nu mice by adoptive transfer. The aim of this study was to examine the molecular mechanism of target (parietal cells) destruction in either thymectomized or II-6 cell-transferred nu/nu mice.

Methods: Expression of Fas, major histocompatibility complex class II, and intercellular adhesion molecule 1 molecules on the gastric mucosa of these mice were immunohistochemically examined. In situ DNA fragmentation in these thymectomized or nu/nu mice was tested by the terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine triphosphate nick end label (TUNEL) method. Moreover, activity of II-6 cells to induce apoptosis was tested by using the 15 mer peptide-pulsed B lymphoma cells, A20.2J, as the target.

Results: A portion of parietal cells in gastritis-bearing thymectomized or nu/nu mice at an early stage expressed Fas, major histocompatibility complex class II, and intercellular adhesion molecule 1 molecules and was TUNEL positive. Fas-ligand message was induced on activated II-6 cells and caused DNA fragmentation of the antigen-pulsed A20.2J cells.

Conclusions: Cognate interaction between Fas antigen on the target and Fas ligand on the effector seems to be one possible mechanism for the target cell destruction in organ-specific autoimmune gastritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Autoimmune Diseases / etiology*
  • Autoimmune Diseases / metabolism
  • Autoimmune Diseases / pathology
  • DNA Fragmentation
  • Fas Ligand Protein
  • Female
  • Gastric Mucosa / pathology
  • Gastritis / etiology*
  • Gastritis / metabolism
  • Gastritis / pathology
  • Histocompatibility Antigens Class II / analysis
  • Intercellular Adhesion Molecule-1 / analysis
  • Male
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred BALB C
  • fas Receptor / physiology*


  • Fas Ligand Protein
  • Fasl protein, mouse
  • Histocompatibility Antigens Class II
  • Membrane Glycoproteins
  • fas Receptor
  • Intercellular Adhesion Molecule-1