title: Upregulation of OX40 ligand on monocytes contributes to early virological control in patients with chronic hepatitis C.
abstract: Dysfunctional hepatitis C virus (HCV) specific CD4(+) T cells are known to contribute to inadequate adaptive immunity in chronic hepatitis C (CHC), although the underlying mechanisms remain largely undefined. In this study, OX40 ligand (OX40L) expression was investigated in 41 treatment-naïve CHC patients, 20 sustained virological responders and 36 healthy subjects. We observed that OX40L expression was significantly upregulated in peripheral monocytes in CHC patients compared with sustained virological responders and healthy subjects. OX40L upregulation correlated significantly with plasma viral load rather than serum alanine aminotransaminase levels. Furthermore, longitudinal analyses indicated that upregulated OX40L expression on monocytes is closely associated with rapid or early virological responses in patients receiving pegylated IFN-α/ribavirin treatment. In vitro, HCV core antigen strongly stimulated monocyte expression of OX40L and blockade of TLR2 signaling significantly downregulated OX40L expression. More importantly, elevated OX40L expression was also shown to be closely associated with elevation of the HCV-specific CD4(+) T-cell response and in vitro blockade of OX40L expressed on monocytes led to impaired CD4(+) T-cell function. These findings, therefore, implicate OX40L expression can be used as a marker to evaluate antiviral treatment efficacy and extend the notion that enhancement of OX40L expression could be a good way for immunotherapy in CHC patients.
authors.affiliation: Institute of Translational Hepatology, Research Center for Biological Therapy, Beijing 302 Hospital, Beijing, P R China.
authors.forename: Ji-Yuan
authors.initials: JY
authors.lastname: Zhang
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Wu
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Feng
authors.forename: Tian-Jun
authors.initials: TJ
authors.lastname: Jiang
authors.forename: Qing-Lei
authors.initials: QL
authors.lastname: Zeng
authors.forename: Xiang-Sheng
authors.initials: XS
authors.lastname: Xu
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.forename: Sa
authors.initials: S
authors.lastname: Lv
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Junliang
authors.initials: J
authors.lastname: Fu
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Wang
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D053278:OX40 Ligand / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015415:Biomarkers; D053278:OX40 Ligand; C089251:TNFSF4 protein, human
keywords: Chronic hepatitis C (HCV); Monocyte; OX40 ligand