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Journal of Virology, December 2002, p. 12423-12434, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12423-12434.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Virus-Specific CD8+ Lymphocytes Share the Same Effector-Memory Phenotype but Exhibit Functional Differences in Acute Hepatitis B and C

Simona Urbani,1 Carolina Boni,1 Gabriele Missale,1 Gianfranco Elia,1 Cristina Cavallo,1 Marco Massari,2 Giovanni Raimondo,3 and Carlo Ferrari1*

Divisione Malattie Infettive ed Epatologia, Azienda Ospedaliera Universitaria di Parma, 43100 Parma,1 Laboratory of Molecular Biology and Section of Hepatology Research, Department of Internal Medicine and Medical Therapy, University of Messina, Messina,3 Unità Operativa Malattie Infettive, Azienda Ospedaliera S. Maria Nuova di Reggio Emilia, 42100 Reggio Emilia, Italy2

Received 17 June 2002/ Accepted 4 September 2002

Hepatitis B and hepatitis C viruses (HBV and HCV) are both noncytopathic and can cause acute and chronic infections of the liver. Although they share tropism for the same organ, development of chronic hepatitis is much more frequent following HCV infection, suggesting different mechanisms of viral persistence. In this study, we show that circulating HBV- and HCV-specific tetramer-positive CD8 cells during the acute phase of hepatitis B and C belong almost entirely to an effector-memory subset (CCR7- CD45RA-). Despite this phenotypic similarity, HBV- and HCV-specific CD8 cells show striking functional differences. HBV-specific tetramer-positive CD8 cells express high perforin content ex vivo, expand vigorously, and display efficient cytotoxic activity and gamma interferon (IFN-{gamma}) production upon peptide stimulation. A comparable degree of functional efficiency is maintained after the resolution of hepatitis B. In contrast, HCV-specific CD8 cells in the acute phase of hepatitis C express significantly lower levels of perforin molecules ex vivo and show depressed CD8 function in terms of proliferation, lytic activity, and IFN-{gamma} production, irrespective of the final outcome of the disease. This defect is transient, because HCV-specific CD8 cells can progressively improve their function in patients with self-limited hepatitis C, while the CD8 function remains persistently depressed in subjects with a chronic evolution.

* Corresponding author. Mailing address: Divisione Malattie Infettive ed Epatologia, Azienda Ospedaliera e Universitaria di Parma, Via Gramsci 14, 43100 Parma, Italy. Phone: 39/521/991056. Fax: 39/521/988706. E-mail: cafer{at}tin.it.

Journal of Virology, December 2002, p. 12423-12434, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12423-12434.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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