Rhesus Macaque Myeloid-Derived Suppressor Cells Demonstrate T Cell Inhibitory Functions and Are Transiently Increased After Vaccination

J Immunol. 2018 Jan 1;200(1):286-294. doi: 10.4049/jimmunol.1701005. Epub 2017 Nov 27.

Abstract

Myeloid-derived suppressor cells (MDSCs) are major regulators of T cell responses in several pathological conditions. Whether MDSCs increase and influence T cell responses in temporary inflammation, such as after vaccine administration, is unknown. Using the rhesus macaque model, which is critical for late-stage vaccine testing, we demonstrate that monocytic (M)-MDSCs and polymorphonuclear (PMN)-MDSCs can be detected using several of the markers used in humans. However, whereas rhesus M-MDSCs lacked expression of CD33, PMN-MDSCs were identified as CD33+ low-density neutrophils. Importantly, both M-MDSCs and PMN-MDSCs showed suppression of T cell proliferation in vitro. The frequency of circulating MDSCs rapidly and transiently increased 24 h after vaccine administration. M-MDSCs infiltrated the vaccine injection site, but not vaccine-draining lymph nodes. This was accompanied by upregulation of genes relevant to MDSCs such as arginase-1, IDO1, PDL1, and IL-10 at the injection site. MDSCs may therefore play a role in locally maintaining immune balance during vaccine-induced inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginase / genetics
  • B7-H1 Antigen / genetics
  • Cell Proliferation
  • Gene Expression Regulation
  • Humans
  • Immune Tolerance
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics
  • Influenza A Virus, H10N8 Subtype / immunology*
  • Influenza Vaccines / immunology*
  • Influenza, Human / immunology*
  • Interleukin-10 / genetics
  • Macaca mulatta
  • Microarray Analysis
  • Myeloid-Derived Suppressor Cells / immunology*
  • Neutrophils / immunology*
  • Orthomyxoviridae Infections / immunology*
  • Sialic Acid Binding Ig-like Lectin 3 / metabolism
  • T-Lymphocytes / immunology*
  • Vaccination

Substances

  • B7-H1 Antigen
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Influenza Vaccines
  • Sialic Acid Binding Ig-like Lectin 3
  • Interleukin-10
  • Arginase
  • arginase I, human