Abstract
Toll-like receptor (TLR) expression on T-cells and the signalling pathways that lead to the production of cytokines may limit antigen-specific T-cell responses. Here, expression of TLR and retinoic acid inducible gene I (RIG-I) on T-cells were evaluated in patients chronically infected with hepatitis C virus (HCV), before and during pegylated interferon-alpha and ribavirin therapy. Expression of TLR2,3,4,7,9 and retinoic acid inducible gene (RIG)-I on different CD4(+) and CD8(+) T-cell sub-populations (naïve: CD45RA(+)CD57(-); central memory: T(CM) CD45RA(-)CD57(-); effector memory: T(EM) CD45RA(-)CD57(+) and terminally differentiated effector memory: T(EMRA) CD45RA(+)CD57(+)) were measured by flow cytometry. TLR7, TLR9 and RIG-I expression on CD4(+) T-cells and RIG-I expression on CD8(+) T-cells was higher in patients than healthy controls. Therapy increased expression of TLR2, TLR4 and TLR9 and this was observed for all T-cell sub-populations. Evaluation of TLR expression at baseline did not identify patients able to achieve sustained virological response following therapy.
Crown Copyright 2010. Published by Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Antigens, CD / biosynthesis
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism*
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CD4-Positive T-Lymphocytes / pathology
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CD8-Positive T-Lymphocytes / drug effects
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism*
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CD8-Positive T-Lymphocytes / pathology
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Cell Separation
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DEAD Box Protein 58
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DEAD-box RNA Helicases / genetics
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DEAD-box RNA Helicases / immunology
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DEAD-box RNA Helicases / metabolism
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Female
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Flow Cytometry
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Hepacivirus / immunology*
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Hepacivirus / pathogenicity
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Hepatitis C, Chronic / drug therapy
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Hepatitis C, Chronic / immunology*
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Hepatitis C, Chronic / pathology
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Hepatitis C, Chronic / physiopathology
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Humans
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Immunologic Memory
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Interferon alpha-2
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Interferon-alpha / administration & dosage
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Male
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Middle Aged
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Polyethylene Glycols / administration & dosage
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Receptors, Immunologic
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Recombinant Proteins
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Ribavirin / administration & dosage
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Toll-Like Receptors / genetics
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Toll-Like Receptors / immunology
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Toll-Like Receptors / metabolism*
Substances
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Antigens, CD
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Interferon alpha-2
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Interferon-alpha
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Receptors, Immunologic
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Recombinant Proteins
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Toll-Like Receptors
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Polyethylene Glycols
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Ribavirin
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RIGI protein, human
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DEAD Box Protein 58
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DEAD-box RNA Helicases
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peginterferon alfa-2a