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Journal of Virology, February 2004, p. 2152-2157, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.2152-2157.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Cytotoxic T Lymphocytes Derived from Patients with Chronic Hepatitis C Virus Infection Kill Bystander Cells via Fas-FasL Interaction

Christel Gremion,1,{dagger} Benno Grabscheid,1,{dagger} Benno Wölk,2 Darius Moradpour,2 Jürg Reichen,3 Werner Pichler,1 and Andreas Cerny4*

Clinic for Rheumatology and Clinical Immunology/Allergology,1 Institute of Clinical Pharmacology, University of Bern, CH-3010 Bern,3 Department of Medicine, Ospedale Regionale di Lugano, CH-6903 Lugano, Switzerland,4 Department of Medicine II, University of Freiburg, D-79106 Freiburg, Germany2

Received 24 June 2003/ Accepted 27 October 2003

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.

* Corresponding author. Mailing address: Department of Medicine, Ospedale Regionale di Lugano, CH-6903 Lugano, Switzerland. Phone: 41 91 811 60 46. Fax: 41 91 811 60 45. E-mail: andreas.cerny{at}bluewin.ch.

{dagger} C.G. and B.G. contributed equally to this work.

Journal of Virology, February 2004, p. 2152-2157, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.2152-2157.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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