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Journal of Virology, August 2008, p. 7567-7577, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.02175-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Differences in Hepatitis C Virus (HCV)-Specific CD8 T-Cell Phenotype during Pegylated Alpha Interferon and Ribavirin Treatment Are Related to Response to Antiviral Therapy in Patients Chronically Infected with HCV{triangledown}

Joana Caetano,1,{dagger} António Martinho,1 Artur Paiva,2 Beatriz Pais,3 Cristina Valente,3 and Cristina Luxo4*

Molecular Biology Laboratory, Histocompatibility Center of Coimbra, Coimbra, Portugal,1 Flow Cytometry Laboratory, Histocompatibility Center of Coimbra, Coimbra, Portugal,2 Department of Infectious Diseases, Hospital Center of Coimbra, Coimbra, Portugal,3 Microbiology Laboratory, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal4

Received 4 October 2007/ Accepted 6 May 2008

CD8 T cells play a major role in antiviral immune responses. Their importance for progression to chronic hepatitis C and response to treatment are still unclear. To address these issues, hepatitis C virus (HCV)-specific CD8 T-cell responses were monitored, at the single-cell level, using HLA class I pentamers specific for HCV core and HCV NS3 epitopes, in 23 chronically infected patients during treatment with pegylated alpha interferon and ribavirin. Patients who presented a sustained-response to therapy had stronger HCV-specific CD8 T-cell responses at all time points studied. Moreover, there were clear differences in the phenotypes of these cells during therapy: in responder patients, terminally differentiated effector cells increased more rapidly, and their frequency was always higher than in nonresponder patients. Sustained-responder patients also showed a higher frequency of HCV-specific CD8 T cells producing cytotoxic factors. Overall, a late and inefficient differentiation process of HCV-specific CD8 T cells might be associated with lack of response to treatment. A better knowledge of the mechanisms underlying this impairment may be important for the development of new therapeutic strategies to maintain, restore, or increase CD8 T-cell effectiveness in chronic HCV infection.

* Corresponding author. Mailing address: Laboratório de Microbiologia, Faculdade de Farmácia, Universidade de Coimbra, Couraça dos Apóstolos, no. 51, R/C Esquerdo, 3000-432 Coimbra, Portugal. Phone: (351) 239852567. Fax: (351) 239852569. E-mail: crisluxo{at}ci.uc.pt

{triangledown} Published ahead of print on 14 May 2008.

{dagger} Present address: Flow Cytometry Section, Hemato-Oncology Laboratory, Portuguese Institute of Oncology of Lisbon, Lisbon, Portugal.

Journal of Virology, August 2008, p. 7567-7577, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.02175-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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