Monocytic myeloid-derived suppressor cells regulate T-cell responses against vaccinia virus.

Published

Journal Article

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.

Full Text

Cited Authors

  • Fortin, C; Yang, Y; Huang, X

Published Date

  • June 2017

Published In

Volume / Issue

  • 47 / 6

Start / End Page

  • 1022 - 1031

PubMed ID

  • 28383204

Pubmed Central ID

  • 28383204

Electronic International Standard Serial Number (EISSN)

  • 1521-4141

International Standard Serial Number (ISSN)

  • 0014-2980

Digital Object Identifier (DOI)

  • 10.1002/eji.201646797

Language

  • eng