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.
Footnotes
This work was supported by funds from the Swedish Medical Council (Vetenskapsrådet) (to K.L.). A.L. was supported by a grant from the China Scholarship Council and a Ph.D. salary grant from Karolinska Institutet. This work is also supported by the European Cooperation in Science and Technology (COST) Action BM1404 European Network of Investigators Triggering Exploratory Research on Myeloid Regulatory Cells. COST is part of the European Union Framework Program Horizon 2020.
The sequences presented in this article have been submitted to Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE98211) under accession number GSE98211.
The online version of this article contains supplemental material.
- Received July 13, 2017.
- Accepted October 28, 2017.
- Copyright © 2017 by The American Association of Immunologists, Inc.