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

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

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.

MeSH terms

  • Animals
  • Antigens, Differentiation / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / immunology
  • Cell Proliferation
  • Friend murine leukemia virus / immunology*
  • Granulocytes / immunology*
  • Granulocytes / metabolism
  • Granulocytes / pathology
  • Leukemia, Experimental / immunology
  • Leukemia, Experimental / metabolism
  • Leukemia, Experimental / pathology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes / immunology
  • Monocytes / metabolism
  • Monocytes / pathology
  • Myeloid-Derived Suppressor Cells / immunology*
  • Myeloid-Derived Suppressor Cells / metabolism
  • Myeloid-Derived Suppressor Cells / pathology
  • Retroviridae Infections / immunology*
  • Retroviridae Infections / metabolism
  • Retroviridae Infections / pathology
  • Tumor Virus Infections / immunology
  • Tumor Virus Infections / metabolism
  • Tumor Virus Infections / pathology

Substances

  • Antigens, Differentiation