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High Level of PD-1 Expression on Hepatitis C Virus (HCV)-Specific CD8⁺ and CD4⁺ T Cells during Acute HCV Infection, Irrespective of Clinical Outcome

Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, 6th Floor, Room 6001, Charlestown, Massachusetts 02129-2000,¹ Med. Klinik I, Universität Hamburg, Germany,² Transplantation Unit, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts 02114,³ Benaroya Research Institute at Virginia Mason, Seattle, Washington,⁴ Lemuel Shattuck Hospital and Tufts University School of Medicine, Boston, Massachusetts,⁵ Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115,⁶ Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114,⁷ Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford OX1 3SY, United Kingdom,⁸ Departmento de Virologia, Instituto Oswaldo Cruz/Fiocruz, Rio de Janeiro, Brazil,⁹ Howard Hughes Medical Institute, Chevy Chase, Maryland,¹⁰

Received 16 November 2007/ Accepted 13 December 2007

We monitored expression of PD-1 (a mediator of T-cell exhaustion and viral persistence) on hepatitis C virus (HCV)-specific CD8⁺ and CD4⁺ T cells from blood and liver during acute and chronic infections and after the resolved infection stage. PD-1 expression on HCV-specific T cells was high early in acute infection irrespective of clinical outcome, and most cells continued to express PD-1 in resolved and chronic stages of infection; intrahepatic expression levels were especially high. Our results suggest that an analysis of PD-1 expression alone is not sufficient to predict infection outcome or to determine T-cell functionality in HCV infection.

Published ahead of print on 26 December 2007.