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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Early interferon therapy for hepatitis C virus infection rescues polyfunctional, long-lived CD8
+
memory T cells
Journal of Virology, Volume 82, No. 20, Year 2008
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Description
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. Copyright © 2008, American Society for Microbiology. All Rights Reserved.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC2566289/bin/supp_82_20_10017__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC2566289/bin/supp_82_20_10017__Supplementary_Table_S1.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC2566289/bin/supp_82_20_10017__JVI01083_08_V1_Figure_S1.zip
https://efashare.b-cdn.net/share/pmc/articles/PMC2566289/bin/supp_82_20_10017__JVI01083_08_V1_Figure_S2.zip
https://efashare.b-cdn.net/share/pmc/articles/PMC2566289/bin/supp_82_20_10017__JVI01083_08_V1_Figure_S3.zip
https://efashare.b-cdn.net/share/pmc/articles/PMC2566289/bin/supp_82_20_10017__Supplementary_Figures_Legends.doc
Authors & Co-Authors
Badr, Gamal
Canada, Montreal
Hopital Saint-luc
Egypt, Asyut
Faculty of Science
Bédard, Nathalie
Canada, Montreal
Hopital Saint-luc
Abdel-Hakeem, Mohamed S.
Canada, Montreal
Hopital Saint-luc
Canada, Montreal
University of Montreal
Trautmann, Lydie
Canada, Montreal
Hopital Saint-luc
Canada, Montreal
Inserm Unit 743
Willems, Bernard E.
Canada, Montreal
Hopital Saint-luc
Canada, Montreal
University of Montreal
Villeneuve, Jean Pierre
Canada, Montreal
Hopital Saint-luc
Canada, Montreal
University of Montreal
Haddad, Elias K.
Canada, Montreal
Hopital Saint-luc
Canada, Montreal
University of Montreal
Canada, Montreal
Inserm Unit 743
Seḱaly, Rafick Pierre
Canada, Montreal
Hopital Saint-luc
Canada, Montreal
University of Montreal
Canada, Montreal
Inserm Unit 743
Bruneau, Julie
Canada, Montreal
Hopital Saint-luc
Canada, Montreal
University of Montreal
Shoukry, Naglaa H.
Canada, Montreal
Hopital Saint-luc
Canada, Montreal
University of Montreal
Statistics
Citations: 151
Authors: 10
Affiliations: 4
Identifiers
Doi:
10.1128/JVI.01083-08
ISSN:
0022538X
Research Areas
Infectious Diseases
Study Design
Randomised Control Trial