TY - JOUR
T1 - Myelin oligodendrocyte glycoprotein induces experimental autoimmune encephalomyelitis in the 'resistant' Brown Norway rat
T2 - Disease susceptibility is determined by MHC and MHC-linked effects on the B cell response
AU - Stefferl, Andreas
AU - Brehm, Uschi
AU - Storch, Maria
AU - Lambracht-Washington, Doris
AU - Bourquin, Carole
AU - Wonigeit, Kurt
AU - Lassmann, Hans
AU - Linington, Christopher
PY - 1999/7/1
Y1 - 1999/7/1
N2 - 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.
AB - 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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M3 - Article
C2 - 10384097
AN - SCOPUS:0033168629
SN - 0022-1767
VL - 163
SP - 40
EP - 49
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -