Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection

Carolina Boni, Paola Fisicaro, Caterina Valdatta, Barbara Amadei, Paola Di Vincenzo, Tiziana Giuberti, Diletta Laccabue, Alessandro Zerbini, Albertina Cavalli, Gabriele Missale, Antonio Bertoletti, Carlo Ferrari

Research output: Contribution to journalArticlepeer-review

Abstract

Dysfunctional CD8+ T cells present in chronic virus infections can express programmed death 1 (PD-1) molecules, and the inhibition of the engagement of PD-1 with its ligand (PD-L1) has been reported to enhance the antiviral function of these T cells. We took advantage of the wide fluctuations in levels of viremia which are typical of chronic hepatitis B virus (HBV) infection to comprehensively analyze the impact of prolonged exposure to different virus quantities on virus-specific T-cell dysfunction and on its reversibility through the blocking of the PD-1/PD-L1 pathway. We confirm that chronic HBV infection has a profound effect on the HBV-specific T-cell repertoire. Despite the use of a comprehensive panel of peptides covering all HBV proteins, HBV-specific T cells were rarely observed directly ex vivo in samples from patients with chronic infection, in contrast to those from patients with acute HBV infection. In chronic HBV infection, virus-specific T cells were detected mainly in patients with lower levels off viremia. These HBV-specific CD8+ T cells expressed PD-1, and their function was improved by the blocking of PD-1/PD-L1 engagement. Thus, a broad spectrum of anti-HBV immunity is expressed by patients with chronic HBV infection and this spectrum is proportional to HBV replication levels and can be improved by blocking the PD-1/PD-L1 pathway. This information may be useful for the design of immunotherapeutic strategies to complement and optimize available antiviral therapies.

Original languageEnglish
Pages (from-to)4215-4225
Number of pages11
JournalJournal of Virology
Volume81
Issue number8
DOIs
Publication statusPublished - Apr 2007

ASJC Scopus subject areas

  • Immunology

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