Abstract
Immunomodulatory cellular subsets, including myeloid-derived suppressor cells (MDSCs) and T regulatory cells (Tregs), contribute to the immunosuppressive tumour microenvironment and are targets of immunotherapy, but their role in retroviral-associated immunosuppression is less well understood. Due to known crosstalk between Tregs and MDSCs in the tumour microenvironment, and also their hypothesized involvement during human immunodeficiency virus/simian immunodeficiency virus infection, studying the interplay between these immune cells during LP-BM5 retrovirus-induced murine AIDS is of interest. IL-10-producing FoxP3+ Tregs expanded after LP-BM5 infection. Following in vivo adoptive transfer of natural Treg (nTreg)-depleted CD4+T-cells, and subsequent LP-BM5 retroviral infection, enriched monocytic MDSCs (M-MDSCs) from these nTreg-depleted mice displayed altered phenotypic subsets. In addition, M-MDSCs from LP-BM5-infected nTreg-depleted mice exhibited increased suppression of T-cell, but not B-cell, responses, compared with M-MDSCs derived from non-depleted LP-BM5-infected controls. Additionally, LP-BM5-induced M-MDSCs modulated the production of IL-10 by FoxP3+ Tregs in vitro. These collective data highlight in vitro and for the first time, to the best of our knowledge, in vivo reciprocal modulation between retroviral-induced M-MDSCs and Tregs, and may provide insight into the immunotherapeutic targeting of such regulatory cells during retroviral infection.
Highlights
Due to their immunosuppressive properties, T regulatory (Treg) cells are immunotherapeutic targets for the treatment of cancer (Dannull et al, 2005; Duraiswamy et al, 2013; Rech et al, 2012; Taieb et al, 2006; Tan et al, 2013)
Following LP-BM5 retroviral infection, FoxP3+CD4+ Tregs expand as early as 1 week post-infection (p.i.), with peak expansion occurring at 2–3 weeks p.i. (Beilharz et al, 2004; Li & Green, 2011)
Because it has been reported that early peak IL-10 levels occur in the first 3 weeks of LP-BM5 infection (Beilharz et al, 2004; Gazzinelli et al, 1992; Uehara et al, 1994) and it was relevant to the studies here, it was determined whether FoxP3+ Tregs produced IL-10 during this time
Summary
Due to their immunosuppressive properties, T regulatory (Treg) cells are immunotherapeutic targets for the treatment of cancer (Dannull et al, 2005; Duraiswamy et al, 2013; Rech et al, 2012; Taieb et al, 2006; Tan et al, 2013). HIV and SIV studies have reported increased (Bandera et al, 2010; Bi et al, 2009; Kinter et al, 2007; Moreno-Fernandez et al, 2012; Schulze Zur Wiesch et al, 2011; Suchard et al, 2010), decreased (Angin et al, 2012; Apoil et al, 2005; Simonetta et al, 2012) or no change (Chevalier et al, 2015) in the Treg compartment. Understanding the role of retrovirus-induced Tregs is critical to determine their potential as immunotherapeutic targets
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