Hepatitis C-specific effector and regulatory CD4 T-cell responses are associated with the outcomes of primary infection.
Identifieur interne : 001456 ( PubMed/Corpus ); précédent : 001455; suivant : 001457Hepatitis C-specific effector and regulatory CD4 T-cell responses are associated with the outcomes of primary infection.
Auteurs : E. Keoshkerian ; M. Hunter ; B. Cameron ; N. Nguyen ; P. Sugden ; R. Bull ; A. Zekry ; L. Maher ; N. Seddiki ; J. Zaunders ; A. Kelleher ; A R LloydSource :
- Journal of viral hepatitis [ 1365-2893 ] ; 2016.
English descriptors
- KwdEn :
- MESH :
- chemical , secretion : Cytokines.
- immunology : CD4-Positive T-Lymphocytes, Hepacivirus, Hepatitis C, T-Lymphocyte Subsets, T-Lymphocytes, Regulatory.
- Adult, Cross-Sectional Studies, Female, Humans, Longitudinal Studies, Male, Treatment Outcome.
Abstract
Clearance of primary hepatitis C virus (HCV) infection has been associated with strong and broadly targeted cellular immune responses. This study aimed to characterize HCV-specific CD4+ effector and regulatory T-cell numbers and cytokine production during primary infection. Antigen-specific CD4+ T-cell responses were investigated in a longitudinal cohort of subjects from pre-infection to postoutcome, including subjects who cleared [n=12] or became chronically infected [n=17]. A cross-sectional cohort with previously cleared, or chronic infection [n=15 for each], was also studied. Peripheral blood mononuclear cells were incubated with HCV antigens and surface stained for T-effector (CD4+CD25(high) CD134+CD39-) and T-regulatory (CD4+CD25(high) CD134+CD39+) markers, and culture supernatants assayed for cytokine production. Contrary to expectations, the breadth and magnitude of the HCV-specific CD4+ T-cell responses were higher in subjects who became chronically infected. Subjects who cleared the virus had HCV-specific CD4+ T-cell responses dominated by effector T cells and produced higher levels of IFN-γ, in contrast to HCV-specific CD4+ T-cell responses dominated by regulatory T cells and more IL-10 production in those who became chronically infected. Better understanding of the role of antigen-specific CD4+ T-cell responses in primary HCV will further define pathogenesis and help guide development of a preventative vaccine.
DOI: 10.1111/jvh.12576
PubMed: 27558465
Links to Exploration step
pubmed:27558465Le document en format XML
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<term>Hepacivirus (immunology)</term>
<term>Hepatitis C (immunology)</term>
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<term>Longitudinal Studies</term>
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<front><div type="abstract" xml:lang="en">Clearance of primary hepatitis C virus (HCV) infection has been associated with strong and broadly targeted cellular immune responses. This study aimed to characterize HCV-specific CD4+ effector and regulatory T-cell numbers and cytokine production during primary infection. Antigen-specific CD4+ T-cell responses were investigated in a longitudinal cohort of subjects from pre-infection to postoutcome, including subjects who cleared [n=12] or became chronically infected [n=17]. A cross-sectional cohort with previously cleared, or chronic infection [n=15 for each], was also studied. Peripheral blood mononuclear cells were incubated with HCV antigens and surface stained for T-effector (CD4+CD25(high) CD134+CD39-) and T-regulatory (CD4+CD25(high) CD134+CD39+) markers, and culture supernatants assayed for cytokine production. Contrary to expectations, the breadth and magnitude of the HCV-specific CD4+ T-cell responses were higher in subjects who became chronically infected. Subjects who cleared the virus had HCV-specific CD4+ T-cell responses dominated by effector T cells and produced higher levels of IFN-γ, in contrast to HCV-specific CD4+ T-cell responses dominated by regulatory T cells and more IL-10 production in those who became chronically infected. Better understanding of the role of antigen-specific CD4+ T-cell responses in primary HCV will further define pathogenesis and help guide development of a preventative vaccine.</div>
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<Abstract><AbstractText>Clearance of primary hepatitis C virus (HCV) infection has been associated with strong and broadly targeted cellular immune responses. This study aimed to characterize HCV-specific CD4+ effector and regulatory T-cell numbers and cytokine production during primary infection. Antigen-specific CD4+ T-cell responses were investigated in a longitudinal cohort of subjects from pre-infection to postoutcome, including subjects who cleared [n=12] or became chronically infected [n=17]. A cross-sectional cohort with previously cleared, or chronic infection [n=15 for each], was also studied. Peripheral blood mononuclear cells were incubated with HCV antigens and surface stained for T-effector (CD4+CD25(high) CD134+CD39-) and T-regulatory (CD4+CD25(high) CD134+CD39+) markers, and culture supernatants assayed for cytokine production. Contrary to expectations, the breadth and magnitude of the HCV-specific CD4+ T-cell responses were higher in subjects who became chronically infected. Subjects who cleared the virus had HCV-specific CD4+ T-cell responses dominated by effector T cells and produced higher levels of IFN-γ, in contrast to HCV-specific CD4+ T-cell responses dominated by regulatory T cells and more IL-10 production in those who became chronically infected. Better understanding of the role of antigen-specific CD4+ T-cell responses in primary HCV will further define pathogenesis and help guide development of a preventative vaccine.</AbstractText>
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