Implications of Lymphocyte Anergy to Glycolipids in Multiple Sclerosis (MS): iNKT Cells May Mediate the MS Infectious Trigger.
Immunogenic lipids may play key roles in host defenses against infection and in generating autoimmune inflammation and organ-specific damage. In multiple sclerosis (MS) there are unequivocal autoimmune features and vulnerability to aggravation or induction by microbial or viral infection. We have found glycolipid-driven anergy of circulating lymphocytes in MS indicating that this immune response is affected in MS and the robust effects of iNKT activation with potent cellular and cytokine activities emphasizes its potential importance. Diverse glycolipids including the endogenous myelin acetylated-galactosylceramides (AcGalCer) can drive activation that could be critical to the inflammatory demyelination in the central nervous system and clinical consequences. The iNKT cells and their invariant or iTCR (Vα24Jα18Vβ11) receptor an innate defense-a discrete immune arm that is separate from peptide-driven acquired immune responses. This offers new possibilities for insight including a likelihood that the pattern recognition of exogenous microbial and myelin immunogens can overlap and cross-react especially in an inflammatory milieu.
Georgia Regents University, Institute of Molecular Medicine and Genetics, Department of Neurology, 1120 15 Street, Augusta, 30912-2620 GA, USA ; National University of Ireland Galway, Department of Microbiology, University Road, Galway, Ireland ; Medical University of South Carolina, Department of Neurosciences, 173 Ashley Avenue, Charleston, SC 29401, USA.
Edward L
EL
Hogan
Georgia Regents University, Institute of Molecular Medicine and Genetics, Department of Neurology, 1120 15 Street, Augusta, 30912-2620 GA, USA ; Ludwik Hirszfeld Institute of Immunology & Experimental Therapy, Polish Academy of Sciences, Laboratory of Signaling Proteins, R. Weigla Street 12, 53-114 Wrocław, Poland.
Maria
M
Podbielska
Department of Life and Physical Sciences, School of Science, Galway-Mayo Institute of Technology, Galway, Ireland.
Joan
J
O'Keeffe
Acetylated galactosylceramides; Anergy; Glycosphingolipids; Multiple sclerosis; iNKT cells