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About the Authors:
Yongjun Sui
* E-mail: [email protected] (YS); [email protected] (JAB)
Affiliation: Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America
ORCID http://orcid.org/0000-0002-1568-4607
Blake Frey
Affiliation: Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America
ORCID http://orcid.org/0000-0003-3003-6904
Yichuan Wang
Affiliation: Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America
Rolf Billeskov
Affiliation: Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America
ORCID http://orcid.org/0000-0003-4533-7304
Shweta Kulkarni
Affiliation: Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America
ORCID http://orcid.org/0000-0002-8092-6422
Katherine McKinnon
Affiliation: Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America
ORCID http://orcid.org/0000-0002-8281-3077
Tracy Rourke
Affiliation: Center for Comparative Medicine, University of California Davis, Davis, CA, United States of America
Linda Fritts
Affiliation: Center for Comparative Medicine, University of California Davis, Davis, CA, United States of America
ORCID http://orcid.org/0000-0003-3703-4629
Christopher J. Miller
Affiliation: Center for Comparative Medicine, University of California Davis, Davis, CA, United States of America
Jay A. Berzofsky
* E-mail: [email protected] (YS); [email protected] (JAB)
Affiliation: Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America
ORCID http://orcid.org/0000-0002-0342-3194Abstract
Myeloid derived suppressor cells (MDSCs), which suppress anti-tumor or anti-viral immune responses, are expanded in the peripheral blood and tissues of patients/animals with cancer or viral infectious diseases. We here show that in chronic SIV infection of Indian rhesus macaques, the frequency of MDSCs in the bone marrow (BM) was paradoxically and unexpectedly decreased, but increased in peripheral blood. Reduction of BM MDSCs was found in both CD14+MDSC and Lin-CD15+MDSC subsets. The reduction of MDSCs correlated with high plasma viral loads and low CD4+ T cell counts, suggesting that depletion of BM MDSCs was associated with SIV/AIDS disease progression. Of note, in SHIVSF162P4-infected macaques, which naturally control viral replication within a few months of infection, the frequency of MDSCs in the bone marrow was unchanged. To investigate the mechanisms by which BM MDSCs were reduced during chronic SIV infection, we tested several hypotheses: depletion due to viral infection, alterations in MDSC trafficking, and/or poor MDSC replenishment. We found that the possible mobilization of MDSCs from BM to...