Demyelination caused by the copper chelator cuprizone halts T cell mediated autoimmune neuroinflammation.
Myelin reactive T cells are central in the development of the autoimmune response leading to CNS destruction in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis (EAE). Investigations on the mechanisms underlying the activation and expansion of myelin reactive T have stressed the importance of non-autoimmune conditions impinging the autoimmune repertoire potentially involved in the disease. Here, we show that CNS injury caused by the toxic cuprizone results in the generation of immunoreactivity towards several myelin components. Paradoxically, exposure to CNS injury does not increase the susceptibility to develop EAE, but render mice protected to the pathogenic autoimmune response against myelin antigens.
Maña
Paula
P
Australian National University Medical School, Canberra Hospital, Australia.
Fordham
Susan A
SA
Staykova
Maria A
MA
Correcha
Manuel
M
Silva
Diego
D
Willenborg
David O
DO
Liñares
David
D
D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D000941:Antigens / Q000276:immunology; D002614:Chelating Agents / Q000633:toxicity; D003471:Cuprizone / Q000633:toxicity*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D006023:Glycoproteins / Q000633:toxicity; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009185:Myelin Proteins / Q000276:immunology; D009186:Myelin Sheath / Q000276:immunology* / Q000473:pathology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000633:toxicity; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000941:Antigens; D002614:Chelating Agents; D016207:Cytokines; D006023:Glycoproteins; D009185:Myelin Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D003471:Cuprizone