title: MHC-class-II are expressed in a subpopulation of human neural stem cells in vitro in an IFNγ-independent fashion and during development.
abstract: Expression of major histocompatibility antigens class-2 (MHC-II) under non-inflammatory conditions is not usually associated with the nervous system. Comparative analysis of immunogenicity of human embryonic/fetal brain-derived neural stem cells (hNSCs) and human mesenchymal stem cells with neurogenic potential from umbilical cord (UC-MSCs) and paediatric adipose tissue (ADSCs), while highlighting differences in their immunogenicity, led us to discover subsets of neural cells co-expressing the neural marker SOX2 and MHC-II antigen in vivo during human CNS development. MHC-II proteins in hNSCs are functional, and differently regulated upon differentiation along different lineages. Mimicking an inflammatory response using the inflammatory cytokine IFNγ induced MHC-II up-regulation in both astrocytes and hNSCs, but not in UC-MSCs and ADSCs, either undifferentiated or differentiated, though IFNγ receptor expression was comparable. Together, hypoimmunogenicity of both UC-MSCs and ADSCs supports their suitability for allogeneic therapy, while significant immunogenicity of hNSCs and their progeny may at least in part underlie negative effects reported in some patients following embryonic neural cell grafts. Crucially, we show for the first time that MHC-II expression in developing human brains is not restricted to microglia as previously suggested, but is present in discrete subsets of neural progenitors and appears to be regulated independently of inflammatory stimuli.
authors.affiliation: Stem Cells and Regenerative Section, UCL Institute of Child Health, London WC1N 1EH, UK.
authors.forename: B
authors.initials: B
authors.lastname: Vagaska
authors.affiliation: Stem Cells and Regenerative Section, UCL Institute of Child Health, London WC1N 1EH, UK.
authors.forename: S E P
authors.initials: SE
authors.lastname: New
authors.affiliation: Anthony Nolan Research Institute, London NW3 2QG, UK.|UCL Cancer Institute, London WC1E 6DD, UK.
authors.forename: C
authors.initials: C
authors.lastname: Alvarez-Gonzalez
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: F
authors.initials: F
authors.lastname: D'Acquisto
authors.affiliation: Anthony Nolan Cell Therapy Centre, Nottingham NG11 8NS, UK.
authors.forename: S G
authors.initials: SG
authors.lastname: Gomez
authors.affiliation: Department of Plastic Surgery, Great Ormond St. Hospital for Children NHS Trust, London WC1N 3JH, UK.
authors.forename: N W
authors.initials: NW
authors.lastname: Bulstrode
authors.affiliation: Anthony Nolan Research Institute, London NW3 2QG, UK.|UCL Cancer Institute, London WC1E 6DD, UK.
authors.forename: A
authors.initials: A
authors.lastname: Madrigal
authors.affiliation: Stem Cells and Regenerative Section, UCL Institute of Child Health, London WC1N 1EH, UK.
authors.forename: P
authors.initials: P
authors.lastname: Ferretti
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D015415:Biomarkers; D002454:Cell Differentiation / Q000235:genetics*; D005312:Fetal Blood / Q000166:cytology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism* / Q000494:pharmacology; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D017471:Receptors, Interferon / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D017471:Receptors, Interferon; D007371:Interferon-gamma