Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6016832 | Experimental Neurology | 2016 | 41 Pages |
Abstract
Previous work by our group showed that transferring bone marrow cells transduced with a self-antigen induced immune tolerance and ameliorated experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). We also found that following retroviral transduction of murine bone marrow (BM) cells, the majority of cells generated and transduced were myeloid-derived suppressor cells (MDSCs). Here, we aimed to determine whether purified antigen-expressing MDSCs have similar therapeutic effects than those of unfractionated BM, and to investigate their potential mechanisms. We performed phenotypic and functional analyses in these cells using the same animal model, and we used purified antigen-expressing MDSCs in preventive and therapeutic approaches. These cells exerted therapeutic effects similar to those of BM cells, which depended upon self-antigen expression. The majority of monocytic (M)-MDSCs expressed the immunosuppressive molecule programmed death ligand-1 (PD-L1), CD80, CD86 and MHC class II molecules. Additionally, the animals infused with antigen-expressing cells exhibited lower percentages of activated T cells and higher percentages of B cells with a regulatory phenotype (B220+Â CD1dhigh CD5+) in the spleen than their respective controls. MDSCs expressing self-antigens, alloantigens or therapeutic transgenes are tolerogenic and can be exploited therapeutically in autoimmune diseases, transplantation and in gene therapy, respectively.
Keywords
TGF-βEAEiNOSLEAIFN-γeGFPMBPGFAPGM-CSFPD-L1i.v.s.c.MFIMOGPD-1PLPTregsMonocytic myeloid-derived suppressor cellsPBS7-aminoactinomycin D7-AADLPSDMEMT helperFBSMDSCsgranulocyte/macrophage colony stimulating factorDulbecco's modified Eagle's mediumMHC class IIROSexperimental autoimmune encephalomyelitisEuropean Unionstandard deviationimmunoglobulin interferon-γinterleukinTransforming Growth Factor Betaimmune toleranceGEEstandard error of the meanIntravenousRoom temperatureInvariant chainsubcutaneousfetal bovine serumCell therapyregulatory B cellsMyeloid-derived suppressor cellsRegulatory T cellsinducible nitric oxide synthaseVascular endothelial growth factorVascular Endothelial Growth Factor (VEGF)Phosphate buffered salinelipopolysaccharideProgrammed death ligand-1MHCmajor histocompatibility complexSEMgeneralized estimating equationbone marrowMultiple sclerosismean fluorescence intensityHematoxylin and EosinGlial fibrillary acidic proteinenhanced green fluorescent proteinMyelin basic proteinProstaglandinsoptical densityReactive oxygen species
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Authors
Silvia Casacuberta-Serra, Carme Costa, Herena Eixarch, MarÃa José Mansilla, Sergio López-Estévez, LluÃs Martorell, Marta Parés, Xavier Montalban, Carmen Espejo, Jordi Barquinero,