Myelin/oligodendrocyte 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, Andre Dautigny, Roland Liblau, Danielle Pham-Dinh

Research output: Contribution to journalArticleAcademicpeer-review

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)544-53
Number of pages10
JournalJournal of Clinical Investigation
Volume112
Issue number4
DOIs
Publication statusPublished - Aug 2003

Cite this

Delarasse, C., Daubas, P., Mars, L. T., Vizler, C., Litzenburger, T., Iglesias, A., ... Pham-Dinh, D. (2003). Myelin/oligodendrocyte glycoprotein-deficient (MOG-deficient) mice reveal lack of immune tolerance to MOG in wild-type mice. Journal of Clinical Investigation, 112(4), 544-53. https://doi.org/10.1172/JCI15861
Delarasse, Cécile ; Daubas, Philippe ; Mars, Lennart T ; Vizler, Csaba ; Litzenburger, Tobias ; Iglesias, Antonio ; Bauer, Jan ; Della Gaspera, Bruno ; Schubart, Anna ; Decker, Laurence ; Dimitri, Dalia ; Roussel, Guy ; Dierich, Andrée ; Amor, Sandra ; Dautigny, Andre ; Liblau, Roland ; Pham-Dinh, Danielle. / Myelin/oligodendrocyte glycoprotein-deficient (MOG-deficient) mice reveal lack of immune tolerance to MOG in wild-type mice. In: Journal of Clinical Investigation. 2003 ; Vol. 112, No. 4. pp. 544-53.
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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.",
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author = "C{\'e}cile Delarasse and Philippe Daubas and Mars, {Lennart T} and Csaba Vizler and Tobias Litzenburger and Antonio Iglesias and Jan Bauer and {Della Gaspera}, Bruno and Anna Schubart and Laurence Decker and Dalia Dimitri and Guy Roussel and Andr{\'e}e Dierich and Sandra Amor and Andre Dautigny and Roland Liblau and Danielle Pham-Dinh",
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Delarasse, C, Daubas, P, Mars, LT, 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/oligodendrocyte glycoprotein-deficient (MOG-deficient) mice reveal lack of immune tolerance to MOG in wild-type mice' Journal of Clinical Investigation, vol. 112, no. 4, pp. 544-53. https://doi.org/10.1172/JCI15861

Myelin/oligodendrocyte glycoprotein-deficient (MOG-deficient) mice reveal lack of immune tolerance to MOG in wild-type mice. / Delarasse, Cécile; Daubas, Philippe; Mars, Lennart T; Vizler, Csaba; Litzenburger, Tobias; Iglesias, Antonio; Bauer, Jan; Della Gaspera, Bruno; Schubart, Anna; Decker, Laurence; Dimitri, Dalia; Roussel, Guy; Dierich, Andrée; Amor, Sandra; Dautigny, Andre; Liblau, Roland; Pham-Dinh, Danielle.

In: Journal of Clinical Investigation, Vol. 112, No. 4, 08.2003, p. 544-53.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Myelin/oligodendrocyte glycoprotein-deficient (MOG-deficient) mice reveal lack of immune tolerance to MOG in wild-type mice

AU - Delarasse, Cécile

AU - Daubas, Philippe

AU - Mars, Lennart T

AU - Vizler, Csaba

AU - Litzenburger, Tobias

AU - Iglesias, Antonio

AU - Bauer, Jan

AU - Della Gaspera, Bruno

AU - Schubart, Anna

AU - Decker, Laurence

AU - Dimitri, Dalia

AU - Roussel, Guy

AU - Dierich, Andrée

AU - Amor, Sandra

AU - Dautigny, Andre

AU - Liblau, Roland

AU - Pham-Dinh, Danielle

PY - 2003/8

Y1 - 2003/8

N2 - 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.

AB - 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.

KW - Animals

KW - B-Lymphocytes

KW - Blotting, Northern

KW - Blotting, Western

KW - Brain

KW - Cell Division

KW - Encephalomyelitis, Autoimmune, Experimental

KW - Female

KW - Immune Tolerance

KW - Immunohistochemistry

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Mutant Strains

KW - Microscopy, Electron

KW - Models, Genetic

KW - Myelin Proteins

KW - Myelin Sheath

KW - Myelin-Associated Glycoprotein

KW - Myelin-Oligodendrocyte Glycoprotein

KW - Peptides

KW - Phenotype

KW - Polymerase Chain Reaction

KW - T-Lymphocytes

KW - Time Factors

KW - Tissue Distribution

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1172/JCI15861

DO - 10.1172/JCI15861

M3 - Article

VL - 112

SP - 544

EP - 553

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 4

ER -