title: Modulation of Tim-3 Expression by Antigen-Dependent and -Independent Factors on T Cells from Patients with Chronic Hepatitis B Virus Infection.
abstract: T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) was up-regulated on viral specific T cells and contributed to T cells exhaustion during chronic hepatitis B virus (HBV) infection. However, modulation of Tim-3 expression was still not fully elucidated. To evaluate the potential viral and inflammatory factors involved in the inductor of Tim-3 expression on T cells, 76 patients with chronic HBV infection (including 40 chronic hepatitis B [CHB] and 36 asymptomatic HBV carriers [AsC]) and 40 of normal controls (NCs) were enrolled in this study. Tim-3 expressions on CD4+and CD8+T cells were assessed in response to HBV-encoding antigens, HBV peptide pools, and common γ-chain (γc) cytokines stimulation by flow cytometry. HBV peptides and anti-CD3/CD28 directly induced Tim-3 expression on T cells. γc cytokines also drive Tim-3 up-regulations on both CD4+and CD8+T cells in patients with chronic HBV infection. However, γc cytokines did not enhance the Tim-3 inductions by either anti-CD3/CD28 or HBV peptides stimulation. Furthermore, γc cytokines-mediated Tim-3 induction could not be abrogated by γc cytokine receptor-neutralizing antibodies. The current results suggested that elevation of Tim-3 expression on T cells could be regulated by both antigen-dependent and -independent manner in patients with chronic HBV infection. The role of γc cytokines in modulation of inhibitory pathway might be evaluated as immunotherapies in humans.
authors.affiliation: Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical UniversityXi'an, China; Department of Ophthalmology and Otorhinolaryngology, Tenth Hospital of PLAWuwei, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Dong
authors.affiliation: Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Yang
authors.affiliation: Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
authors.forename: Lin-Xu
authors.initials: LX
authors.lastname: Wang
authors.affiliation: Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Epidemiology, School of Public Health, Fourth Military Medical University Xi'an, China.
authors.forename: An-Hui
authors.initials: AH
authors.lastname: Wang
authors.affiliation: Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
authors.forename: Chun-Qiu
authors.initials: CQ
authors.lastname: Hao
authors.affiliation: Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
authors.forename: Huan-Jun
authors.initials: HJ
authors.lastname: Shen
authors.affiliation: Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
authors.forename: Chang-Xing
authors.initials: CX
authors.lastname: Huang
authors.affiliation: Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
authors.forename: Jian-Qi
authors.initials: JQ
authors.lastname: Lian
mesh_terms: D000328:Adult; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D000072597:Hepatitis A Virus Cellular Receptor 2 / Q000378:metabolism*; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000821:virology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000382:microbiology*; D055815:Young Adult
chemical_list: D000956:Antigens, Viral; D016207:Cytokines; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins
keywords: T cell receptor; T-cell immunoglobulin domain and mucin domain-containing molecule-3; common γ-chain cytokines; hepatitis B virus; immunomodulation