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

Ang Lin, Frank Liang, Elizabeth A. Thompson, Maria Vono, Sebastian Ols, Gustaf Lindgren, Kimberly Hassett, Hugh Salter, Giuseppe Ciaramella and Karin Loré
J Immunol November 27, 2017, ji1701005; DOI: https://doi.org/10.4049/jimmunol.1701005
Ang Lin
*Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, 171 76 Stockholm, Sweden;
†Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden;
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Frank Liang
*Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, 171 76 Stockholm, Sweden;
†Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden;
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Elizabeth A. Thompson
*Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, 171 76 Stockholm, Sweden;
†Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden;
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Maria Vono
*Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, 171 76 Stockholm, Sweden;
†Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden;
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Sebastian Ols
*Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, 171 76 Stockholm, Sweden;
†Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden;
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Gustaf Lindgren
*Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, 171 76 Stockholm, Sweden;
†Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden;
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Kimberly Hassett
‡Valera LLC, Cambridge, MA 02141; and
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Hugh Salter
§Department of Clinical Neuroscience, Karolinska Institutet, 171 76 Stockholm, Sweden
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Giuseppe Ciaramella
‡Valera LLC, Cambridge, MA 02141; and
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Karin Loré
*Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, 171 76 Stockholm, Sweden;
†Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden;
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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.
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The Journal of Immunology: 209 (1)
The Journal of Immunology
Vol. 209, Issue 1
1 Jul 2022
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Rhesus Macaque Myeloid-Derived Suppressor Cells Demonstrate T Cell Inhibitory Functions and Are Transiently Increased after Vaccination
Ang Lin, Frank Liang, Elizabeth A. Thompson, Maria Vono, Sebastian Ols, Gustaf Lindgren, Kimberly Hassett, Hugh Salter, Giuseppe Ciaramella, Karin Loré
The Journal of Immunology November 27, 2017, ji1701005; DOI: 10.4049/jimmunol.1701005

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Rhesus Macaque Myeloid-Derived Suppressor Cells Demonstrate T Cell Inhibitory Functions and Are Transiently Increased after Vaccination
Ang Lin, Frank Liang, Elizabeth A. Thompson, Maria Vono, Sebastian Ols, Gustaf Lindgren, Kimberly Hassett, Hugh Salter, Giuseppe Ciaramella, Karin Loré
The Journal of Immunology November 27, 2017, ji1701005; DOI: 10.4049/jimmunol.1701005
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