title: Invariant Natural Killer T-cell anergy to endogenous myelin acetyl-glycolipids in multiple sclerosis.
abstract: To extend our studies on glycolipid-reactive invariant Natural Killer T-cell (iNKT-cell) function in multiple sclerosis (MS), we investigated the stimulatory activities of two myelin-derived glycolipids that are poly-acetylated derivatives of β-galactosylceramide designated as fast-migrating cerebrosides (FMC) by thin-layer chromatography. In healthy subjects, FMC stimulation of peripheral blood cells significantly expanded iNKT-cells similar to α-GalCer and induced significant increases in Th1, Th2 and Th17 cytokines. In marked contrast, MS patients failed to respond to FMCs or to α-GalCer stimulation indicating an anergic response. We propose that myelin-derived FMC glycolipids stimulate iNKT-cell responses in vivo and this is blocked in MS.
authors.affiliation: Department of Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland.
authors.forename: Carol M
authors.initials: CM
authors.lastname: Gately
authors.forename: Maria
authors.initials: M
authors.lastname: Podbielska
authors.forename: Timothy
authors.initials: T
authors.lastname: Counihan
authors.forename: Michael
authors.initials: M
authors.lastname: Hennessy
authors.forename: Teresa
authors.initials: T
authors.lastname: Leahy
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Moran
authors.forename: Edward L
authors.initials: EL
authors.lastname: Hogan
authors.forename: Joan
authors.initials: J
authors.lastname: O'Keeffe
mesh_terms: D000328:Adult; D000368:Aged; D002240:Carbohydrate Sequence; D002554:Cerebrosides / Q000737:chemistry / Q000378:metabolism; D017635:Clonal Anergy / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D005699:Galactosylceramides / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020528:Multiple Sclerosis, Chronic Progressive / Q000276:immunology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology*; D009186:Myelin Sheath / Q000378:metabolism*; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism*; D015213:Neuroimmunomodulation / Q000276:immunology; D055815:Young Adult
chemical_list: D002554:Cerebrosides; D005699:Galactosylceramides; C493154:alpha-galactosylceramide