title: CD3(bright)CD56(+) T cells associate with pegylated interferon-alpha treatment nonresponse in chronic hepatitis B patients.
abstract: Chronic hepatitis B (CHB) infection is a serious and prevalent health concern worldwide, and the development of effective drugs and strategies to combat this disease is urgently needed. Currently, pegylated interferon-alpha (peg-IFNα) and nucleoside/nucleotide analogues (NA) are the most commonly prescribed treatments. However, sustained response rates in patients remain low, and the reasons are not well understood. Here, we observed that CHB patients preferentially harbored CD3(bright)CD56(+) T cells, a newly identified CD56(+) T cell population. Patients with this unique T cell population exhibited relatively poor responses to peg-IFNα treatment. CD3(bright)CD56(+) T cells expressed remarkably high levels of the inhibitory molecule NKG2A as well as low levels of CD8. Even if patients were systematically treated with peg-IFNα, CD3(bright)CD56(+) T cells remained in an inhibitory state throughout treatment and exhibited suppressed antiviral function. Furthermore, peg-IFNα treatment rapidly increased inhibitory TIM-3 expression on CD3(bright)CD56(+) T cells, which negatively correlated with IFNγ production and might have led to their dysfunction. This study identified a novel CD3(bright)CD56(+) T cell population preferentially shown in CHB patients, and indicated that the presence of CD3(bright)CD56(+) T cells in CHB patients may be useful as a new indicator associated with poor therapeutic responses to peg-IFNα treatment.
authors.affiliation: Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Science and Medical Center, University of Science and Technology of China, Hefei 230027, People's Republic of China.
authors.forename: Chuang
authors.initials: C
authors.lastname: Guo
authors.affiliation: Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Science and Medical Center, University of Science and Technology of China, Hefei 230027, People's Republic of 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 Science and Medical Center, University of Science and Technology of China, Hefei 230027, People's Republic of China.|Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui, People's Republic of China.
authors.forename: Binqing
authors.initials: B
authors.lastname: Fu
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of 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 Science and Medical Center, University of Science and Technology of China, Hefei 230027, People's Republic of China.
authors.forename: Yongyan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Science and Medical Center, University of Science and Technology of China, Hefei 230027, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Ni
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of 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 Science and Medical Center, University of Science and Technology of China, Hefei 230027, People's Republic of China.|Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of 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 Science and Medical Center, University of Science and Technology of China, Hefei 230027, People's Republic of China.|Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui, People's Republic of 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 Science and Medical Center, University of Science and Technology of China, Hefei 230027, People's Republic of China.|Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui, People's Republic of China.
authors.forename: Haiming
authors.initials: H
authors.lastname: Wei
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000737:chemistry / Q000627:therapeutic use; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D019002:CD56 Antigen / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism; D005260:Female; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000187:drug effects; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000276:immunology / Q000378:metabolism; D017063:Outcome Assessment, Health Care / Q000379:methods; D011092:Polyethylene Glycols / Q000737:chemistry; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D017252:CD3 Complex; D019002:CD56 Antigen; D016827:CD8 Antigens; D016898:Interferon-alpha; D055654:NK Cell Lectin-Like Receptor Subfamily C; D011092:Polyethylene Glycols