| First Author | Fortin C | Year | 2017 |
| Journal | Eur J Immunol | Volume | 47 |
| Issue | 6 | Pages | 1022-1031 |
| PubMed ID | 28383204 | Mgi Jnum | J:252105 |
| Mgi Id | MGI:5923734 | Doi | 10.1002/eji.201646797 |
| Citation | Fortin C, et al. (2017) Monocytic myeloid-derived suppressor cells regulate T-cell responses against vaccinia virus. Eur J Immunol 47(6):1022-1031 |
| abstractText | 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-gamma 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. |
