blockade of immunosuppressive cytokines restores nk cell antiviral function in chronic hepatitis b virus infection免疫抑制细胞因子的封锁恢复nk细胞在慢性乙型肝炎病毒感染抗病毒功能.pdf
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Blockade of Immunosuppressive Cytokines Restores NK
Cell Antiviral Function in Chronic Hepatitis B Virus
Infection
1,2 1 3 3 1 1
Dimitra Peppa , Lorenzo Micco , Alia Javaid , Patrick T. F. Kennedy , Anna Schurich , Claire Dunn ,
1 1 1,4 4 2 1,2,3
Celeste Pallant , Gidon Ellis , Pooja Khanna , Geoffrey Dusheiko , Richard J. Gilson , Mala K. Maini *
1 Division of Infection and Immunity, UCL, London, United Kingdom, 2 Centre for Sexual Health and HIV Research, UCL, London, United Kingdom, 3 Centre for Digestive
Disease, Barts and The London School of Medicine and Dentistry, London, United Kingdom, 4 Centre for Hepatology, Hampstead Campus, Royal Free University College
Medical School, London, United Kingdom
Abstract
NK cells are enriched in the liver, constituting around a third of intrahepatic lymphocytes. We have previously demonstrated
that they upregulate the death ligand TRAIL in patients with chronic hepatitis B virus infection (CHB), allowing them to kill
hepatocytes bearing TRAIL receptors. In this study we investigated whether, in addition to their pathogenic role, NK cells
have antiviral potential in CHB. We characterised NK cell subsets and effector function in 64 patients with CHB compared to
31 healthy controls. We found that, in contrast to their upregulated TRAIL expression and maintenance of cytolytic function,
NK cells had a markedly impaired capacity to produce IFN-c in CHB. This functional dichotomy of NK cells could be
recapitulated in vitro by exposure to the immunosuppressive cytokine IL-10, which was induced in p
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