Format

Send to

Choose Destination
Retrovirology. 2017 Aug 23;14(1):42. doi: 10.1186/s12977-017-0364-3.

Granulocytic myeloid-derived suppressor cells suppress virus-specific CD8+ T cell responses during acute Friend retrovirus infection.

Author information

1
Institute of Virology, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
2
Research Group Bioinformatics, Faculty of Biology, University of Duisburg-Essen, Essen, Germany.
3
Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
4
Department of Immunobiology, Yale School of Medicine, Yale University, New Haven, CT, USA.
5
Institute of Virology, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany. gennadiy.zelinskyy@uni-due.de.

Abstract

BACKGROUND:

Myeloid-derived suppressor cells (MDSCs) can suppress T cell responses in several different diseases. Previously these suppressive cells were observed to expand in HIV patients and in a mouse retrovirus model, yet their suppressive effect on virus-specific CD8+ T cells in vitro and in vivo has not been characterized thus far.

RESULTS:

We used the Friend retrovirus (FV) model to demonstrate that MDSCs expand and become activated during the late phase of acute FV infection. Only the subpopulation of granulocytic MDSCs (gMDSCs) but not monocytic MDSC suppressed virus-specific CD8+ T cell proliferation and function in vitro. gMDSCs expressed arginase 1, high levels of the inhibitory ligand PD-L1 and the ATP dephosphorylating enzyme CD39 on the cell surface upon infection. All three molecules were involved in the suppressive effect of the gMDSCs in vitro. MDSC depletion experiments in FV-infected mice revealed that they restrict virus-specific CD8+ T cell responses and thus affect the immune control of chronic retroviruses in vivo.

CONCLUSIONS:

Our study demonstrates that MDSCs become activated and expand during the acute phase of retrovirus infection. Their suppressive activity on virus-specific CD8+ T cells may contribute to T cell dysfunction and the development of chronic infection.

KEYWORDS:

Arginase; CD8+ T cells; Friend virus; MDSC; PD-L1

PMID:
28835242
PMCID:
PMC5569525
DOI:
10.1186/s12977-017-0364-3
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center