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CNS autoimmunity mediated by pathogenic T cell and antibody responses: immunogenetics, pathogenesis and therapy of MOG-induced EAE

Objective

To define susceptibility genes for myelin-oligodendrocyte-glycoprotein (MOG) induced rat experimental autoimmune encephalomyelitis with the aim to study relevance of these also in multiple sclerosis (MS). This may allow definition of new targets for therapy.
To explore tolerogenic strategies and in this MS-like experimental disease driven by a complex interplay between pathogenic T and B cell responses.
To examine the role of MOG-specific autoimmune responses in the pathogenesis of MS.

MS is the most common inflammatory demyelinating disease of the central nervous system (CNS) in Europe. With a prevalence of 1/1000 and affecting mainly young adults this represents a major socio-economic burden on the community. However, the etiology of MS is unknown and there is no satisfactory treatment available. There is a clear genetic predisposition to develop MS although environmental factors also play an important role in disease induction. The identification of those genetic loci that determine susceptibility to MS and how they interact with environment is essential for the development of novel therapeutic and prophylactic measures to counter this disease. Current concepts on the etiopathogenesis of MS suggest that it is a purely T cell mediated autoimmune disease. This is based on observations made in an animal model, experimental autoimmune encephalomyelitis (EAE), induced by immunization with myelin basic protein. However, several observations suggest that humoral immune effector mechanisms are critically involved in lesion formation, in particular in the primary demyelination which is a characteristic feature of MS lesions. A potential target for such an autoantibody response has been identified as the myelin oligodendrocyte glycoprotein (MOG). This antigen is unique among myelin antigens since it contains both encephalitogenic T cell epitopes and pathogenic B cell epitopes. Our groups have shown that synergy between these two immune effector mechanisms results in a form of chronic relapsing EAE (CREAE) which mimics the clinical course and pathology of MS. Genetic susceptibility and resistance to MOG induced EAE differs fundamentally from that established in previous models of EAE.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

Karolinska Institute
Address

171 76 Stockholm
Sweden

Participants (2)

Max-Planck-Gesellschaft zur Förderungder Wissenschaften e.V.
Germany
Address
Am Klopferspitz 18A
82152 Martinsried
UNIVERSITY OF VIENNA
Austria
Address
17,Waehringer Guerter, 18-20
1010 Wien