Essential roles of the Fas ligand in the development of hepatitis.
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.
Kondo
T
T
Osaka Bioscience Institute, Japan.
Suda
T
T
Fukuyama
H
H
Adachi
M
M
Nagata
S
S
D000818:Animals; D003602:Cytotoxicity, Immunologic; D004731:Endotoxins / Q000494:pharmacology; D053222:Fas Ligand Protein; D006501:Hepatic Encephalopathy / Q000209:etiology* / Q000276:immunology / Q000401:mortality / Q000517:prevention & control; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D012995:Solubility; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic; D019014:fas Receptor / Q000378:metabolism* / Q000494:pharmacology
D004731:Endotoxins; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D006514:Hepatitis B Surface Antigens; D008562:Membrane Glycoproteins; D019014:fas Receptor