title: Monocytic myeloid-derived suppressor cells regulate T-cell responses against vaccinia virus.
abstract: 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.
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Carl
authors.initials: C
authors.lastname: Fortin
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, NC, USA.|Division of Hematologic Malignancies and Cellular Therapy, Department of Immunology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Yiping
authors.identifier: 0000-0002-1291-7460
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Xiaopei
authors.initials: X
authors.lastname: Huang
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology; D007694:Killer Cells, Natural; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D000072737:Myeloid-Derived Suppressor Cells / Q000187:drug effects / Q000276:immunology*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D054390:Receptors, CCR2 / Q000172:deficiency / Q000378:metabolism; D014615:Vaccinia / Q000821:virology; D014616:Vaccinia virus / Q000276:immunology*
chemical_list: C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2; D009569:Nitric Oxide; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse
keywords: Immune regulation; Monocytes; T cells