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Hepatitis C-specific effector and regulatory CD4 T-cell responses are associated with the outcomes of primary infection.

Hepatitis C-specific effector and regulatory CD4 T-cell responses are associated with the outcomes of primary infection.
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Keoshkerian E, Hunter M, Cameron B, Nguyen N, Sugden P, Bull R, Zekry A, Maher L, Seddiki N, Zaunders J, Kelleher A, Lloyd AR, ,


Keoshkerian E, Hunter M, Cameron B, Nguyen N, Sugden P, Bull R, Zekry A, Maher L, Seddiki N, Zaunders J, Kelleher A, Lloyd AR, , (click to view)

Keoshkerian E, Hunter M, Cameron B, Nguyen N, Sugden P, Bull R, Zekry A, Maher L, Seddiki N, Zaunders J, Kelleher A, Lloyd AR, ,

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Journal of viral hepatitis 2016 8 25() doi 10.1111/jvh.12576

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.

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