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KMID : 0578320140370010066
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Molecules and Cells
2014 Volume.37 No. 1 p.66 ~ p.73
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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
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Qing-Lei Zeng
Bin Yang
Hong-Qi Sun
Guo-Hua Feng
Lei Jin
Zheng-Sheng Zou
Zheng Zhang
Zhang Ji-Yuan
Wang Fu-Sheng
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Abstract
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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 -arginine treatment . 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.
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KEYWORD
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arginase-1, hepatitis C virus, L-arginine, myeloid-derived suppressor cell, TCR ζ chain
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