title: TCRγδ(+)CD4(-)CD8(-) T cells suppress the CD8(+) T-cell response to hepatitis B virus peptides, and are associated with viral control in chronic hepatitis B.
abstract: The immune mechanisms underlying failure to achieve hepatitis B e antigen (HBeAg) seroconversion associated with viral control in chronic hepatitis B (CHB) remain unclear. Here we investigated the role of CD4(-)CD8(-) T (double-negative T; DNT) cells including TCRαβ(+) DNT (αβ DNT) and TCRγδ(+) DNT (γδ DNT) cells. Frequencies of circulating DNT cell subsets were measured by flow cytometry in a retrospective cohort of 51 telbivudine-treated HBeAg-positive CHB patients, 25 immune tolerant carriers (IT), 33 inactive carriers (IC), and 37 healthy controls (HC). We found that γδ DNT cell frequencies did not significantly change during treatment, being lower at baseline (P = 0.019) in patients with HBeAg seroconversion after 52 weeks of antiviral therapy (n = 20) than in those without (n = 31), and higher in the total CHB and IT than IC and HC groups (P<0.001). αβ DNT cell frequencies were similar for all groups. In vitro, γδ DNT cells suppressed HBV core peptide-stimulated interferon-γ and tumor necrosis factor-α production in TCRαβ(+)CD8(+) T cells, which may require cell-cell contact, and could be partially reversed by anti-NKG2A. These findings suggest that γδ DNT cells limit CD8(+) T cell response to HBV, and may impede HBeAg seroconversion in CHB.
authors.affiliation: Hepatology Unit and Key Lab for Organ Failure Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Guangzhou, China.
authors.forename: Qintao
authors.initials: Q
authors.lastname: Lai
authors.affiliation: Hepatology Unit and Key Lab for Organ Failure Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Guangzhou, China ; Department of Infectious Diseases, Kunming General Hospital of PLA, Kunming, China.
authors.forename: Shiwu
authors.initials: S
authors.lastname: Ma
authors.affiliation: Hepatology Unit and Key Lab for Organ Failure Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Guangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ge
authors.affiliation: Hepatology Unit and Key Lab for Organ Failure Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Guangzhou, China.
authors.forename: Zuxiong
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Hepatology Unit and Key Lab for Organ Failure Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Guangzhou, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Huang
authors.affiliation: Hepatology Unit and Key Lab for Organ Failure Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Guangzhou, China ; Department of immunology, Basic Medicine School, Southern Medical University, Auckland City Hospital, Auckland, New Zealand.
authors.forename: Xiaotao
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Hepatology Unit and Key Lab for Organ Failure Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Guangzhou, China.
authors.forename: Yongyin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Hepatology Unit and Key Lab for Organ Failure Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Guangzhou, China.
authors.forename: Mingxia
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Hepatology Unit and Key Lab for Organ Failure Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Guangzhou, China.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Hepatology Unit and Key Lab for Organ Failure Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Guangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Hepatology Unit and Key Lab for Organ Failure Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Guangzhou, China ; The New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand.
authors.forename: William G H
authors.initials: WG
authors.lastname: Abbott
authors.affiliation: Hepatology Unit and Key Lab for Organ Failure Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Guangzhou, China.
authors.forename: Jinlin
authors.initials: J
authors.lastname: Hou
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006679:HIV Seropositivity / Q000150:complications / Q000276:immunology / Q000821:virology; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000187:drug effects / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000821:virology; D018655:Lymphocyte Count; D008297:Male; D010455:Peptides / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D000077712:Telbivudine; D013936:Thymidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D010455:Peptides; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000077712:Telbivudine; D013936:Thymidine