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: Carol M Gately, Maria Podbielska, Timothy Counihan, Michael Hennessy, Teresa Leahy, Anthony P Moran, Edward L Hogan, Joan O'Keeffe
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 259 Issue 1-2 Pg. 1-7 (Jun 15 2013) ISSN: 1872-8421 [Electronic] Netherlands
• PMID: 23537888 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Cerebrosides
• Galactosylceramides
• alpha-galactosylceramide

Topics

• Adult
• Aged
• Carbohydrate Sequence
• Cerebrosides (chemistry, metabolism)
• Clonal Anergy (immunology)
• Female
• Flow Cytometry
• Galactosylceramides (chemistry, metabolism)
• Humans
• Male
• Middle Aged
• Molecular Sequence Data
• Multiple Sclerosis, Chronic Progressive (immunology)
• Multiple Sclerosis, Relapsing-Remitting (immunology)
• Myelin Sheath (metabolism)
• Natural Killer T-Cells (immunology, metabolism)
• Neuroimmunomodulation (immunology)
• Young Adult