Abstract
BackgroundMyeloid-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.ResultsWe 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.ConclusionsOur 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.
Highlights
Myeloid-derived suppressor cells (MDSCs) can suppress T cell responses in several different diseases
MDSCs were characterized according to recommendations for the phenotypic definition of these cells [38,39,40] CD11b+ cells were gated from live, single-cell splenocytes, which were negative for CD3, CD19, NK1.1, and Ter119 lineage markers
These CD11b+ myeloid cells were divided according to their expression of Ly6C and Ly6G in monocytic and granulocytic MDSCs (Fig. 1a). mMDSCs and gMDSCs were detectible in naïve mice, but their frequencies were below 0.3% per one million nucleated splenocytes
Summary
Myeloid-derived suppressor cells (MDSCs) can suppress T cell responses in several different diseases 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 far. The suppressive effects of MDSCs on virus-specific cytotoxic C D8+ T cell responses was not analyzed and the role of MDSCs for the establishment of a chronic retroviral infection remains elusive. These important questions have been addressed in the current study using the Friend virus (FV) mouse model
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