Myelin oligodendrocyte glycoprotein induces experimental autoimmune encephalomyelitis in the 'resistant' Brown Norway rat

Disease susceptibility is determined by MHC and MHC-linked effects on the B cell response

Andreas Stefferl, Uschi Brehm, Maria Storch, Doris Lambracht-Washington, Carole Bourquin, Kurt Wonigeit, Hans Lassmann, Christopher Linington

Research output: Contribution to journalArticle

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Abstract

Experimental autoimmune encephalomyelitis (EAE) induced by active immunization with the myelin oligodendrocyte glycoprotein (MOG) is an Ab- mediated, T cell-dependent autoimmune disease that replicates the inflammatory demyelinating pathology of multiple sclerosis. We report that disease susceptibility and severity are determined by MHC and MHC-linked effects on the MOG-specific B cell response that mediate severe clinical EAE in the EAE-resistant Brown Norway (BN) rat. Immunization with the extracellular domain of MOG in CFA induced fulminant clinical disease associated with widespread demyelination and with an inflammatory infiltrate containing large numbers of polymorphonuclear cells and eosinophils within 10 days of immunization. To analyze the effects of the MHC (RT1 system) we compared BN (RT1 (n)) rats with Lewis (LEW) (RT1 (l)) and two reciprocal MHC congenic strains, LEW.1N (RT1(n)) and BN.1L (RT1 (l)). This comparison revealed that disease severity and clinical course were strongly influenced by the haplotype that modulated the pathogenic MOG-specific autoantibody response. The intra-MHC recombinant congenic strain LEW.1R38 demonstrated that gene loci located both within the centromeric segment of the MHC containing classical class I and class II genes and within the telomeric RT1.M region containing the MOG gene are involved in determining Ab production and disease susceptibility. This study indicates that the current T cell-centered interpretation of MHC-mediated effects on disease susceptibility must be reassessed in multiple sclerosis and other autoimmune diseases in which autoantibody is involved in disease pathogenesis.

Original languageEnglish (US)
Pages (from-to)40-49
Number of pages10
JournalJournal of Immunology
Volume163
Issue number1
StatePublished - Jul 1 1999

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Myelin-Oligodendrocyte Glycoprotein
Autoimmune Experimental Encephalomyelitis
Disease Susceptibility
B-Lymphocytes
Autoantibodies
Autoimmune Diseases
Multiple Sclerosis
Immunization
T-Lymphocytes
MHC Class II Genes
Demyelinating Diseases
Norway
Eosinophils
Haplotypes
Genes
Vaccination
Cell Count
Pathology

ASJC Scopus subject areas

  • Immunology

Cite this

Myelin oligodendrocyte glycoprotein induces experimental autoimmune encephalomyelitis in the 'resistant' Brown Norway rat : Disease susceptibility is determined by MHC and MHC-linked effects on the B cell response. / Stefferl, Andreas; Brehm, Uschi; Storch, Maria; Lambracht-Washington, Doris; Bourquin, Carole; Wonigeit, Kurt; Lassmann, Hans; Linington, Christopher.

In: Journal of Immunology, Vol. 163, No. 1, 01.07.1999, p. 40-49.

Research output: Contribution to journalArticle

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abstract = "Experimental autoimmune encephalomyelitis (EAE) induced by active immunization with the myelin oligodendrocyte glycoprotein (MOG) is an Ab- mediated, T cell-dependent autoimmune disease that replicates the inflammatory demyelinating pathology of multiple sclerosis. We report that disease susceptibility and severity are determined by MHC and MHC-linked effects on the MOG-specific B cell response that mediate severe clinical EAE in the EAE-resistant Brown Norway (BN) rat. Immunization with the extracellular domain of MOG in CFA induced fulminant clinical disease associated with widespread demyelination and with an inflammatory infiltrate containing large numbers of polymorphonuclear cells and eosinophils within 10 days of immunization. To analyze the effects of the MHC (RT1 system) we compared BN (RT1 (n)) rats with Lewis (LEW) (RT1 (l)) and two reciprocal MHC congenic strains, LEW.1N (RT1(n)) and BN.1L (RT1 (l)). This comparison revealed that disease severity and clinical course were strongly influenced by the haplotype that modulated the pathogenic MOG-specific autoantibody response. The intra-MHC recombinant congenic strain LEW.1R38 demonstrated that gene loci located both within the centromeric segment of the MHC containing classical class I and class II genes and within the telomeric RT1.M region containing the MOG gene are involved in determining Ab production and disease susceptibility. This study indicates that the current T cell-centered interpretation of MHC-mediated effects on disease susceptibility must be reassessed in multiple sclerosis and other autoimmune diseases in which autoantibody is involved in disease pathogenesis.",
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