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Multiple sclerosis (MS) is one of the most intensively studied immune-based inflammatory diseases (IMID) of the human central nervous system. Experimental autoimmune encephalomyelitis (EAE) is the elected animal model of MS in which immunopathogenic mechanisms are investigated and the efficacy of new therapies can be tested. However, of the many new therapies that showed promising effects in EAE models only very few were found effective in patients. One possible explanation is the immunological gap between the laboratory mouse and rat strains in which EAE is modeled and the MS patient. In this publication we discuss how EAE models in non-human primates can bridge this gap. Not only is the immune system of non-human primates more closely related to humans, but the EAE models in these species also offer unique possibilities for preclinical research.

The recombinant human (rh) myelin/oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) model in the common marmoset is characterized by 100% disease incidence, a chronic disease course, and a variable time interval between immunization and neurological impairment. We investigated whether monkeys with fast and slow disease progression display different anti-MOG T or B cell responses and analyzed the underlying pathogenic mechanism(s). The results show that fast progressor monkeys display a significantly wider specificity diversification of anti-MOG T cells at necropsy than slow progressors, especially against MOG(34-56) and MOG(74-96). MOG(34-56) emerged as a critical encephalitogenic peptide, inducing severe neurological disease and multiple lesions with inflammation, demyelination, and axonal injury in the CNS. Although EAE was not observed in MOG(74-96)-immunized monkeys, weak T cell responses against MOG(34-56) and low grade CNS pathology were detected. When these cases received a booster immunization with MOG(34-56) in IFA, full-blown EAE developed. MOG(34-56)-reactive T cells expressed CD3, CD4, or CD8 and CD56, but not CD16. Moreover, MOG(34-56)-specific T cell lines displayed specific cytotoxic activity against peptide-pulsed B cell lines. The phenotype and cytotoxic activity suggest that these cells are NK-CTL. These results support the concept that cytotoxic cells may play a role in the pathogenesis of multiple sclerosis.