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Hepatitis C‐specific effector and regulatory CD 4 T‐cell responses are associated with the outcomes of primary infection
Author(s) -
Keoshkerian E.,
Hunter M.,
Cameron B.,
Nguyen N.,
Sugden P.,
Bull R.,
Zekry A.,
Maher L.,
Seddiki N.,
Zaunders J.,
Kelleher A.,
Lloyd A. R.
Publication year - 2016
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.12576
Subject(s) - immunology , cytokine , peripheral blood mononuclear cell , effector , antigen , hepatitis c virus , t cell , biology , immune system , virology , medicine , virus , in vitro , biochemistry
Summary 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 CD 4+ effector and regulatory T‐cell numbers and cytokine production during primary infection. Antigen‐specific CD 4+ 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 ( CD 4+ CD 25 high CD 134+ CD 39‐) and T‐regulatory ( CD 4+ CD 25 high CD 134+ CD 39+) markers, and culture supernatants assayed for cytokine production. Contrary to expectations, the breadth and magnitude of the HCV ‐specific CD 4+ T‐cell responses were higher in subjects who became chronically infected. Subjects who cleared the virus had HCV ‐specific CD 4+ T‐cell responses dominated by effector T cells and produced higher levels of IFN ‐γ, in contrast to HCV ‐specific CD 4+ 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 CD 4+ T‐cell responses in primary HCV will further define pathogenesis and help guide development of a preventative vaccine.