Hepatitis C Virus-Induced Myeloid-Derived Suppressor Cells Regulate T-cell Differentiation and Function via the Signal Transducer and Activator of Transcription 3 Pathway

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T cells play a pivotal role in controlling viral infection; however, the precise mechanisms responsible for regulating T‐cell differentiation and function during infections are incompletely understood. In this study, we demonstrated an expansion of myeloid‐derived suppressor cells (MDSC s), in particular the monocytic MDSC s (M‐MDSC s; CD 14+ CD 33+ CD 11b+ HLA ‐DR −/low), in patients with chronic hepatitis C virus (HCV ) infection. Notably, HCV ‐induced M‐MDSC s express high levels of phosphorylated signal transducer and activator of transcription 3 (pSTAT 3) and interleukin‐10 (IL ‐10) compared with healthy subjects. Blocking STAT 3 signalling reduced HCV ‐mediated M‐MDSC expansion and decreased IL ‐10 expression. Importantly, we observed a significant increase in the numbers of CD 4+ CD 25+ Foxp3+ regulatory T (Treg) cells following incubation of healthy peripheral blood mononuclear cells (PBMC s) with MDSC s derived from HCV ‐infected patients or treated with HCV core protein. In addition, depletion of MDSC s from PBMC s led to a significant reduction of Foxp3+ Treg cells developed during chronic HCV infection. Moreover, depletion of MDSC s from PBMC s significantly increased interferon‐γ production by CD 4+ T effector (Teff) cells derived from HCV patients. These results suggest that HCV ‐induced MDSC s promote Treg cell development and inhibit Teff cell function, suggesting a novel mechanism for T‐cell regulation and a new strategy for immunotherapy against human viral diseases.