Myelin/oligodendarocyte glycoprotein-deficient (MOG-deficient) mice reveal lack of immune tolerance to MOG in wild-type mice

Cécile Delarasse, Philippe Daubas, Lennart T. Mars, Csaba Vizler, Tobias Litzenburger, Antonio Iglesias, Jan Bauer, Bruno Della Gaspera, Anna Schubart, Laurence Decker, Dalia Dimitri, Guy Roussel, Andrée Dierich, Sandra Amor, André Dautigny, Roland Liblau, Danielle Pham-Dinh

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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.

Original languageEnglish
Pages (from-to)544-553
Number of pages10
JournalJournal of Clinical Investigation
Volume112
Issue number4
DOIs
Publication statusPublished - Aug 2003

ASJC Scopus subject areas

  • Medicine(all)

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    Delarasse, C., Daubas, P., Mars, L. T., Vizler, C., Litzenburger, T., Iglesias, A., Bauer, J., Della Gaspera, B., Schubart, A., Decker, L., Dimitri, D., Roussel, G., Dierich, A., Amor, S., Dautigny, A., Liblau, R., & Pham-Dinh, D. (2003). Myelin/oligodendarocyte glycoprotein-deficient (MOG-deficient) mice reveal lack of immune tolerance to MOG in wild-type mice. Journal of Clinical Investigation, 112(4), 544-553. https://doi.org/10.1172/JCI15861