title: Myelin/oligodendrocyte glycoprotein-deficient (MOG-deficient) mice reveal lack of immune tolerance to MOG in wild-type mice.
abstract: We studied the immunological basis for the very potent encephalitogenicity of myelin/oligodendrocyte glycoprotein (MOG), a minor component of myelin in the CNS that is widely used to induce experimental autoimmune encephalomyelitis (EAE). For this purpose, we generated a mutant mouse lacking a functional mog gene. This MOG-deficient mouse presents no clinical or histological abnormalities, permitting us to directly assess the role of MOG as a target autoantigen in EAE. In contrast to WT mice, which developed severe EAE following immunization with whole myelin, MOG-deficient mice had a mild phenotype, demonstrating that the anti-MOG response is a major pathogenic component of the autoimmune response directed against myelin. Moreover, while MOG transcripts are expressed in lymphoid organs in minute amounts, both MOG-deficient and WT mice show similar T and B cell responses against the extracellular domain of MOG, including the immunodominant MOG 35-55 T cell epitope. Furthermore, no differences in the fine specificity of the T cell responses to overlapping peptides covering the complete mouse MOG sequence were observed between MOG+/+ and MOG-/- mice. In addition, upon adoptive transfer, MOG-specific T cells from WT mice and those from MOG-deficient mice are equally pathogenic. This total lack of immune tolerance to MOG in WT C57BL/6 mice may be responsible for the high pathogenicity of the anti-MOG immune response as well as the high susceptibility of most animal strains to MOG-induced EAE.
authors.affiliation: INSERM U546, Hôpital de la Salpêtrière, 105 Boulevard de l'Hôpital, Paris 75013, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Delarasse
authors.forename: Philippe
authors.initials: P
authors.lastname: Daubas
authors.forename: Lennart T
authors.initials: LT
authors.lastname: Mars
authors.forename: Csaba
authors.initials: C
authors.lastname: Vizler
authors.forename: Tobias
authors.initials: T
authors.lastname: Litzenburger
authors.forename: Antonio
authors.initials: A
authors.lastname: Iglesias
authors.forename: Jan
authors.initials: J
authors.lastname: Bauer
authors.forename: Bruno
authors.initials: B
authors.lastname: Della Gaspera
authors.forename: Anna
authors.initials: A
authors.lastname: Schubart
authors.forename: Laurence
authors.initials: L
authors.lastname: Decker
authors.forename: Dalia
authors.initials: D
authors.lastname: Dimitri
authors.forename: Guy
authors.initials: G
authors.lastname: Roussel
authors.forename: Andrée
authors.initials: A
authors.lastname: Dierich
authors.forename: Sandra
authors.initials: S
authors.lastname: Amor
authors.forename: Andre
authors.initials: A
authors.lastname: Dautigny
authors.forename: Roland
authors.initials: R
authors.lastname: Liblau
authors.forename: Danielle
authors.initials: D
authors.lastname: Pham-Dinh
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D002455:Cell Division; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology; D005260:Female; D007108:Immune Tolerance; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D008957:Models, Genetic; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000378:metabolism; D018992:Myelin-Associated Glycoprotein / Q000235:genetics* / Q000502:physiology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010455:Peptides