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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

发布:2017-08-28约字共10页下载文档
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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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