title: Myeloid-derived suppressor cells are associated with viral persistence and downregulation of TCR ζ chain expression on CD8(+) T cells in chronic hepatitis C patients.
abstract: Myeloid-derived suppressor cells (MDSCs) play an important role in impairing the function of T cells. We characterized MDSCs in two chronic hepatitis C (CHC) cohorts: a cross-sectional group that included 61 treatment-naive patients with CHC, 14 rapid virologic response (RVR) cases and 22 early virologic response (EVR) cases; and a longitudinal group of 13 cases of RVR and 10 cases of EVR after pegylated-interferon-α/ribavirin treatment for genotype 1b HCV infection. Liver samples from 32 CHC patients and six healthy controls were subjected to immunohistochemical analysis. MDSCs frequency in treatment-naive CHC was significantly higher than in RVR, EVR, or healthy subjects and was positively correlated with HCV RNA. Patients infected with HCV genotype 2a had a significantly higher frequency of MDSCs than those infected with genotype 1b. Decreased T cell receptor (TCR) ζ expression on CD8(+) T cells was significantly associated with an increased frequency of MDSCs in treatment-naive CHC patients and was restored by L-arginine treatment in vitro. Increased numbers of liver arginase-1(+) cells were closely associated with the histological activity index in CHC. The TCR ζ chain was significantly downregulated on hepatic CD8(+) T cells in CHC. During antiviral follow up, MDSCs frequency in peripheral blood mononuclear cells was directly correlated with the HCV RNA load in the plasma and inversely correlated with TCR ζ chain expression in CD8(+) T cells in both RVR and EVR cases. Notably, the RVR group had a higher frequency of MDSCs at baseline than the EVR group. Collectively, this study provides evidence that MDSCs might be associated with HCV persistence and downregulation of CD8 ζ chain expression.
authors.affiliation: Research Center for Biological Therapy, Beijing 302 Hospital, Peking University Health Science Center, Beijing, China.
authors.forename: Qing-Lei
authors.initials: QL
authors.lastname: Zeng
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.forename: Hong-Qi
authors.initials: HQ
authors.lastname: Sun
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Feng
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.forename: Zheng-Sheng
authors.initials: ZS
authors.lastname: Zou
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Ji-Yuan
authors.initials: JY
authors.lastname: Zhang
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D001119:Arginase / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D016022:Case-Control Studies; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology* / Q000821:virology; D012367:RNA, Viral / Q000097:blood; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D011948:Receptors, Antigen, T-Cell; C121913:antigen T cell receptor, eta-kappa; C574619:ARG1 protein, human; D001119:Arginase