Journal article
Early Interferon Therapy for Hepatitis C Virus Infection Rescues Polyfunctional, Long-Lived CD8+ Memory T Cells
Journal of virology, v 82(20), pp 10017-10031
30 Jul 2008
PMID: 18667516
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The majority of acute hepatitis C virus (HCV) infections progress to chronicity and progressive liver damage. Alpha interferon (IFN-α) antiviral therapy achieves the highest rate of success when IFN-α is administered early during the acute phase, but the underlying mechanisms are unknown. We used a panel of major histocompatibility complex class I tetramers to monitor the phenotypic and functional signatures of HCV-specific T cells during acute HCV infection with different infection outcomes and during early IFN therapy. We demonstrate that spontaneous resolution correlates with the early development of polyfunctional (IFN-γ- and IL-2-producing and CD107a
+
) virus-specific CD8
+
T cells. These polyfunctional T cells are distinguished by the expression of CD127 and Bcl-2 and represent a transitional memory T-cell subset that exhibits the phenotypic and functional signatures of both central and effector memory T cells. In contrast, HCV-specific CD8
+
T cells in acute infections evolving to chronicity expressed low levels of CD127 and Bcl-2, exhibited diminished proliferation and cytokine production, and eventually disappeared from the periphery. Early therapeutic intervention with pegylated IFN-α rescued polyfunctional memory T cells expressing high levels of CD127 and Bcl-2. These cells were detectable for up to 1 year following discontinuation of therapy. Our results suggest that the polyfunctionality of HCV-specific T cells can be predictive of the outcome of acute HCV infection and that early therapeutic intervention can reconstitute the pool of long-lived polyfunctional memory T cells.
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Details
- Title
- Early Interferon Therapy for Hepatitis C Virus Infection Rescues Polyfunctional, Long-Lived CD8+ Memory T Cells
- Creators
- Gamal Badr - Centre Hospitalier de l’Université de MontréalNathalie Bédard - Centre Hospitalier de l’Université de MontréalMohamed S. Abdel-Hakeem - Centre Hospitalier de l’Université de MontréalLydie Trautmann - Centre Hospitalier de l’Université de MontréalBernard Willems - Centre Hospitalier de l’Université de MontréalJean-Pierre Villeneuve - Centre Hospitalier de l’Université de MontréalElias K. Haddad - Assiut UniversityRafick P. Sékaly - Centre Hospitalier de l’Université de MontréalJulie Bruneau - Université de MontréalNaglaa H. Shoukry - Centre Hospitalier de l’Université de Montréal
- Publication Details
- Journal of virology, v 82(20), pp 10017-10031
- Publisher
- American Society for Microbiology (ASM)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine); Drexel University
- Web of Science ID
- WOS:000260109100019
- Scopus ID
- 2-s2.0-53749106026
- Other Identifier
- 991020099618704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Virology