Myelin/oligodendrocyte glycoprotein-deficient (MOG-deficient) mice reveal lack of immune tolerance to MOG in wild-type mice.
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.
Delarasse
Cécile
C
INSERM U546, Hôpital de la Salpêtrière, 105 Boulevard de l'Hôpital, Paris 75013, France.
Daubas
Philippe
P
Mars
Lennart T
LT
Vizler
Csaba
C
Litzenburger
Tobias
T
Iglesias
Antonio
A
Bauer
Jan
J
Della Gaspera
Bruno
B
Schubart
Anna
A
Decker
Laurence
L
Dimitri
Dalia
D
Roussel
Guy
G
Dierich
Andrée
A
Amor
Sandra
S
Dautigny
Andre
A
Liblau
Roland
R
Pham-Dinh
Danielle
D
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
C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010455:Peptides