Cytotoxic T lymphocytes derived from patients with chronic hepatitis C virus infection kill bystander cells via Fas-FasL interaction.
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.
Gremion
Christel
C
Clinic for Rheumatology and Clinical Immunology/Allergology, University of Bern, CH-3010 Bern, Switzerland.
Grabscheid
Benno
B
Wölk
Benno
B
Moradpour
Darius
D
Reichen
Jürg
J
Pichler
Werner
W
Cerny
Andreas
A
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
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D014764:Viral Proteins; D019014:fas Receptor