Essential roles of the Fas ligand in the development of hepatitis

Nat Med. 1997 Apr;3(4):409-13. doi: 10.1038/nm0497-409.


The Fas ligand (FasL) is expressed in activated T cells and induces apoptosis in Fas-bearing cells. A cytotoxic T lymphocyte (CTL) clone specific for hepatitis B surface antigen (HBsAg) causes an acute liver disease in HBsAg transgenic mice. Here we observed that the CTL clone killed hepatocytes expressing HBsAg in a Fas-dependent manner. Administration of the soluble form of Fas into HBsAg transgenic mice prevented the CTL-induced liver disease. In the second model, mice were primed with Propionibacterium acnes. A subsequent challenge with lipopolysaccharide (LPS) killed the mice by inducing liver injury. Neutralization of FasL rescued the mice from LPS-induced mortality, and Fas-null mice were resistant to LPS-induced mortality. These results suggest that FasL has an essential role in the development of hepatitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytotoxicity, Immunologic
  • Endotoxins / pharmacology
  • Fas Ligand Protein
  • Hepatic Encephalopathy / etiology*
  • Hepatic Encephalopathy / immunology
  • Hepatic Encephalopathy / mortality
  • Hepatic Encephalopathy / prevention & control
  • Hepatitis B Surface Antigens / genetics
  • Hepatitis B Surface Antigens / immunology
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Transgenic
  • Solubility
  • Survival Analysis
  • T-Lymphocytes, Cytotoxic
  • fas Receptor / metabolism*
  • fas Receptor / pharmacology


  • Endotoxins
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Hepatitis B Surface Antigens
  • Membrane Glycoproteins
  • fas Receptor