title: NKp30+NK cells are associated with HBV control during pegylated-interferon-alpha-2b therapy of chronic hepatitis B.
abstract: A pressing need exists for improved therapeutic options for chronic hepatitis B (CHB). Pegylated-interferon-alpha (Peg-IFN-α) achieves sustained off-treatment responses in many cases because of its direct anti-viral effects and regulation of the immune response. However, non-responsiveness to Peg-IFN-α is frequent, and the mechanism is poorly understood. In this study, we found that the frequency and absolute number of NKp30+natural killer (NK) cells increased markedly, accompanied by enhanced CD107a and IFN-γ production, during Peg-IFN-α-2b monotherapy or combination therapy with adefovir dipivoxil in patients with CHB, especially in responders. The responders and non-responders differed in the frequency of polyfunctional IFN-γ+CD107+NK cells. In addition, the increase in NKp30+NK cells was negatively correlated with the HBV viral load and plasma HBeAg. Moreover, it was found that IL-15 may contribute to the up-regulation of NKp30 on the NK cells, and this up-regulation was not induced in vitro by Peg-IFN-α-2b alone. However, in the non-responders, these NKp30+NK cells were dysfunctional because of increased NKG2A expression, which partly explains the inactivation of NKp30+NK cells and the reduced capacity of these cells to produce antiviral cytokines. These findings may provide a new mechanism to explain the variable efficacy of Peg-IFN-α-2b therapy.
authors.affiliation: Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Shen
authors.affiliation: Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.|Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Binqing
authors.initials: B
authors.lastname: Fu
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University and Chaohu Hospital of Anhui Medical University, Hefei, Anhui, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Chuang
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University and Chaohu Hospital of Anhui Medical University, Hefei, Anhui, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.|Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University and Chaohu Hospital of Anhui Medical University, Hefei, Anhui, China.
authors.forename: Jiabin
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.|Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui 230027, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
authors.affiliation: Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.|Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Haiming
authors.initials: H
authors.lastname: Wei
mesh_terms: D000328:Adult; D005260:Female; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D055628:Natural Cytotoxicity Triggering Receptor 3; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage
chemical_list: C573415:IFNG protein, human; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D052118:Lysosomal-Associated Membrane Protein 1; C431710:NCR3 protein, human; D055628:Natural Cytotoxicity Triggering Receptor 3; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D007371:Interferon-gamma; C417083:peginterferon alfa-2b