Hepatitis C‐specific effector and regulatory CD4 T‐cell responses are associated with the outcomes of primary infection
Identifieur interne : 001469 ( Main/Exploration ); précédent : 001468; suivant : 001470Hepatitis C‐specific effector and regulatory CD4 T‐cell responses are associated with the outcomes of primary infection
Auteurs : E. Keoshkerian [Australie] ; M. Hunter [Australie] ; B. Cameron [Australie] ; N. Nguyen [Australie] ; P. Sugden [Australie] ; R. Bull [Australie] ; A. Zekry [Australie] ; L. Maher [Australie] ; N. Seddiki [France] ; J. Zaunders [Australie] ; A. Kelleher [Australie] ; A. R. Lloyd [Australie] ; Kate Dolan ; Paul Haber ; William Rawlinson ; Carla Treloar ; Greg Dore ; Fabio LucianiSource :
- Journal of Viral Hepatitis [ 1352-0504 ] ; 2016-12.
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+CD25highCD134+CD39‐) and T‐regulatory (CD4+CD25highCD134+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.
Url:
DOI: 10.1111/jvh.12576
Affiliations:
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<front><div type="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+CD25highCD134+CD39‐) and T‐regulatory (CD4+CD25highCD134+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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