LAUSR

Vaccinia virus (VV) can potently activate NK‐ and T‐cell responses, leading to efficient viral control and generation of long‐lasting protective immunity. However, immune responses against viral infections are often tightly controlled to avoid collateral damage and systemic inflammation. We have previously shown that granulocytic myeloid‐derived suppressor cells (g‐MDSCs) can suppress the NK‐cell response to VV infection. It remains unknown what regulates T‐cell responses to VV infection in vivo. In this study, we first showed that monocytic MDSCs (m‐MDSCs), but not g‐MDSCs, from VV‐infected mice could directly suppress CD4+ and CD8+ T‐cell activation in vitro. We then demonstrated that defective recruitment of m‐MDSCs to the site of VV infection in CCR2−/− mice enhanced VV‐specific CD8+ T‐cell response and that adoptive transfer of m‐MDSCs into VV‐infected mice suppressed VV‐specific CD8+ T‐cell activation, leading to a delay in viral clearance. Mechanistically, we further showed that T‐cell suppression by m‐MDSCs is mediated by indication of iNOS and production of NO upon VV infection, and that IFN‐γ is required for activation of m‐MDSCs. Collectively, our results highlight a critical role for m‐MDSCs in regulating T‐cell responses against VV infection and may suggest potential strategies using m‐MDSCs to modulate T‐cell responses during viral infections.