title: Restored circulating invariant NKT cells are associated with viral control in patients with chronic hepatitis B.
abstract: Invariant NKT (iNKT) cells are involved in the pathogenesis of various infectious diseases. However, their role in hepatitis B virus (HBV) infection is not fully understood, especially in human species. In this study, 35 chronic hepatitis B (CHB) patients, 25 inactive carriers (IC) and 36 healthy controls (HC) were enrolled and the proportions of circulating iNKT cells in fresh isolated peripheral blood mononuclear cells (PBMC) were detected by flow cytometry. A longitudinal analysis was also conducted in 19 CHB patients who received antiviral therapy with telbivudine. Thereafter, the immune functions of iNKT cells were evaluated by cytokine secretion and a two-chamber technique. The median frequency of circulating iNKT cells in CHB patients (0.13%) was lower than that in HC (0.24%, P = 0.01) and IC (0.19%, P = 0.02), and increased significantly during antiviral therapy with telbivudine (P = 0.0176). The expressions of CC chemokine receptor 5 (CCR5) and CCR6 were dramatically higher on iNKT cells (82.83%±9.87%, 67.67%±16.83% respectively) than on conventional T cells (30.5%±5.65%, 14.02%±5.92%, both P<0.001) in CHB patients. Furthermore, iNKT cells could migrate toward the CC chemokine ligand 5. Patients with a high ratio (≥1.0) of CD4-/CD4+ iNKT cells at baseline had a higher rate (58.33%) of HBeAg seroconversion than those with a low ratio (<1.0, 0%, P = 0.0174). In conclusion, there is a low frequency of peripheral iNKT cells in CHB patients, which increases to normal levels with viral control. The ratio of CD4-/CD4+ iNKT cells at baseline may be a useful predictor for HBeAg seroconversion in CHB patients on telbivudine therapy.
authors.affiliation: Institute of Hepatology and Key Lab for Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Xiaotao
authors.initials: X
authors.lastname: Jiang
authors.forename: Mingxia
authors.initials: M
authors.lastname: Zhang
authors.forename: Qintao
authors.initials: Q
authors.lastname: Lai
authors.forename: Xuan
authors.initials: X
authors.lastname: Huang
authors.forename: Yongyin
authors.initials: Y
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: William G H
authors.initials: WG
authors.lastname: Abbott
authors.forename: Shiwu
authors.initials: S
authors.lastname: Ma
authors.forename: Jinlin
authors.initials: J
authors.lastname: Hou
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000187:drug effects / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D009705:Nucleosides / Q000494:pharmacology / Q000627:therapeutic use; D011744:Pyrimidinones / Q000494:pharmacology / Q000627:therapeutic use; D019713:Receptors, CCR5 / Q000378:metabolism; D054399:Receptors, CCR6 / Q000378:metabolism; D000077712:Telbivudine; D013936:Thymidine / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: C106311:CCR6 protein, human; D016207:Cytokines; D006513:Hepatitis B e Antigens; D009705:Nucleosides; D011744:Pyrimidinones; D019713:Receptors, CCR5; D054399:Receptors, CCR6; D000077712:Telbivudine; D013936:Thymidine