Selective Involvement of the Checkpoint Regulator VISTA in Suppression of B-Cell,but Not T-Cell,Responsiveness by Monocytic Myeloid-Derived Suppressor Cells from Mice Infected with an Immunodeficiency-Causing Retrovirus |
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| Authors: | Kathy A. Green Li Wang Randolph J. Noelle William R. Green |
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| Affiliation: | aGeisel School of Medicine at Dartmouth, Department of Microbiology and Immunology, and Norris Cotton Cancer Center, Lebanon, New Hampshire, USA;bMedical College of Wisconsin, Department of Microbiology and Molecular Genetics, Milwaukee, Wisconsin, USA;cDepartment of Nephrology and Transplantation, Medical Research Council Centre for Transplantation, King''s College London Guy''s Hospital, London, United Kingdom |
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| Abstract: | Inhibition of T-cell responses in tumor microenvironments by myeloid-derived suppressor cells (MDSCs) is widely accepted. We demonstrated augmentation of monocytic MDSCs whose suppression of not only T-cell, but also B-cell, responsiveness paralleled the immunodeficiency during LP-BM5 retrovirus infection. MDSCs inhibited T cells by inducible nitric oxide synthase (iNOS)/nitric oxide (NO), but uniquely, inhibition of B cells was ∼50% dependent each on iNOS/NO and the MDSC-expressed negative-checkpoint regulator VISTA. Blockade with a combination of iNOS/NO and VISTA caused additive or synergistic abrogation of MDSC-mediated suppression of B-cell responsiveness. |
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