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http://dx.doi.org/10.14348/molcells.2014.2282

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)
Publication Information
Molecules and Cells / v.37, no.1, 2014 , pp. 66-73 More about this Journal
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
arginase-1; hepatitis C virus; L-arginine; myeloid-derived suppressor cell; TCR ${\zeta}$ chain;
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