title: Subpopulations of M-MDSCs from mice infected by an immunodeficiency-causing retrovirus and their differential suppression of T- vs B-cell responses.
abstract: Monocytic (CD11b(+)Ly6G(±/Lo)Ly6C(+)) myeloid derived suppressor cells (M-MDSCs) expand following murine retroviral LP-BM5 infection and suppress ex vivo polyclonal T-cell and B-cell responses. M-MDSCs 3 weeks post LP-BM5 infection have decreased suppression of T-cell, but not B-cell, responses and alterations in the degree of iNOS/NO dependence of suppression. M-MDSCs from LP-BM5 infected mice were sorted into four quadrant populations (Ly6C/CD11b density): all quadrants suppressed B-cell responses, but only M-MDSCs expressing the highest levels of Ly6C and CD11b (Q2) significantly suppressed T-cell responses. Further subdivision of this Q2 population revealed the Ly6C(+/Hi) M-MDSC subpopulation as the most suppressive, inhibiting T- and B-cell responses in a full, or partially, iNOS/NO-dependent manner, respectively. In contrast, the lower/moderate levels of suppression by the Ly6C(+/Lo) and Ly6C(+/Mid) M-MDSC Q2 subpopulations, whether versus T- and/or B-cells, displayed little/no iNOS dependency for suppression. These results highlight differential phenotypic and functional immunosuppressive M-MDSC subsets in a retroviral immunodeficiency model.
authors: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
authors: Megan A
authors: MA
authors: O'Connor
authors: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
authors: Whitney W
authors: WW
authors: Fu
authors: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
authors: Kathy A
authors: KA
authors: Green
authors: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA; Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA. Electronic address: William.R.Green@dartmouth.edu.
authors: William R
authors: WR
authors: Green
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D056747:Immunomodulation; D016130:Immunophenotyping; D051379:Mice; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000276:immunology*; D012192:Retroviridae Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; D000950:Antigens, Ly; D039481:CD11b Antigen; C494192:Ly-6C antigen, mouse; D019707:Receptors, Chemokine; C036763:monocyte-macrophage differentiation antigen
keywords: LP-BM5; Myeloid derived suppressor cells; Retrovirus