Immunology 2016 5 5() doi 10.1111/imm.12616
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 (MDSCs), in particular the monocytic MDSCs (M-MDSCs; CD14(+) CD33(+) CD11b(+) HLA-DR(-/low) ), in patients with chronic hepatitis C virus (HCV) infection. Notably, HCV-induced M-MDSCs express high levels of phosphorylated signal transducer and activator of transcription 3 (pSTAT3) and interleukin-10 (IL-10) compared to healthy subjects (HS). Blocking STAT3 signaling reduced HCV-mediated M-MDSC expansion and decreased IL-10 expression. Importantly, we observed a significant increase in the numbers of CD4(+) CD25(+) Foxp3(+) T regulatory (Treg) cells following incubation of healthy peripheral blood mononuclear cells (PBMCs) with MDSCs derived from HCV-infected patients or treated with HCV core protein. In addition, depletion of MDSCs from PBMCs led to a significant reduction of Foxp3(+) Treg cells developed during chronic HCV infection. Moreover, depletion of MDSCs from PBMCs significantly increased IFN-γ production by CD4(+) T effector (Teff) cells derived from HCV patients. These results suggest that HCV-induced MDSCs 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. This article is protected by copyright. All rights reserved.