title: Reciprocal relationship of T regulatory cells and monocytic myeloid-derived suppressor cells in LP-BM5 murine retrovirus-induced immunodeficiency.
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.
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.
authors.forename: Megan A
authors.initials: MA
authors.lastname: O'Connor
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Vella
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.|Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Green
mesh_terms: D000818:Animals; D007153:Immunologic Deficiency Syndromes / Q000473:pathology* / Q000821:virology; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology*; D012190:Retroviridae / Q000502:physiology*; D012192:Retroviridae Infections / Q000276:immunology* / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*