title: Cytotoxic T lymphocytes derived from patients with chronic hepatitis C virus infection kill bystander cells via Fas-FasL interaction.
abstract: The role of Fas-mediated lysis of hepatocytes in hepatitis C virus (HCV)-induced injury is frequently discussed. We therefore analyzed the effect of the number of HCV antigen-expressing cells, the mode of antigen presentation, and the number of cytotoxic T lymphocytes in a coculture system mimicking cellular components of the liver. Here, we show that endogenously processed HCV proteins are capable of inducing bystander killing. We further demonstrate that 0.8 to 1.5% of cells presenting HCV antigens suffice to induce lysis of 10 to 29% of bystander cells, suggesting that the mechanism may be operative at low fractions of infected versus uninfected hepatocytes in vivo. Our data underscore the role of the Fas pathway in HCV-related liver injury and support the exploration of Fas-based treatment strategies for patients with chronic hepatitis C virus infection.
authors.affiliation: Clinic for Rheumatology and Clinical Immunology/Allergology, University of Bern, CH-3010 Bern, Switzerland.
authors.forename: Christel
authors.initials: C
authors.lastname: Gremion
authors.forename: Benno
authors.initials: B
authors.lastname: Grabscheid
authors.forename: Benno
authors.initials: B
authors.lastname: Wölk
authors.forename: Darius
authors.initials: D
authors.lastname: Moradpour
authors.forename: Jürg
authors.initials: J
authors.lastname: Reichen
authors.forename: Werner
authors.initials: W
authors.lastname: Pichler
authors.forename: Andreas
authors.initials: A
authors.lastname: Cerny
mesh_terms: D000818:Animals; D017209:Apoptosis; D024201:Bystander Effect; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000821:virology; D022781:Hepatocytes / Q000276:immunology* / Q000821:virology; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D014764:Viral Proteins; D019014:fas Receptor