Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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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

  • Zeng, Qing-Lei (Research Center for Biological Therapy, Beijing 302 Hospital, Peking University Health Science Center) ;
  • Yang, Bin (Department of Interventional Radiology, Beijing 302 Hospital) ;
  • Sun, Hong-Qi (Department of Infectious Diseases, Zhengzhou Sixth People's Hospital) ;
  • Feng, Guo-Hua (Research Center for Biological Therapy, Beijing 302 Hospital, Peking University Health Science Center) ;
  • Jin, Lei (The Institute of Translational Hepatology) ;
  • Zou, Zheng-Sheng (Non-infectious Liver Disease Diagnosis and Treatment Center, Beijing 302 Hospital) ;
  • Zhang, Zheng (The Institute of Translational Hepatology) ;
  • Zhang, Ji-Yuan (The Institute of Translational Hepatology) ;
  • Wang, Fu-Sheng (Research Center for Biological Therapy, Beijing 302 Hospital, Peking University Health Science Center)
  • Received : 2013.10.07
  • Accepted : 2013.12.03
  • Published : 2014.01.31
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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-${\alpha}$/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) ${\zeta}$ 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 ${\zeta}$ 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 ${\zeta}$ 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 ${\zeta}$ chain expression.

Keywords

References

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