Optimization of an animal model of experimental autoimmune encephalomyelitis achieved with a multiple MOG 35–55peptide in C57BL6/J strain of mice

Abstract

The severity of the experimental autoimmune encephalomyelitis (EAE) induced by peptide myelin oligodendrocyte glycoprotein 35–55(pMOG 35–55) is thought to be predominantly influenced by the major histocompatibility complex (MHC), so that C57BL6/J mice, on H2 b strain, were only mildly sick. However, it remains unclear as to how non-MHC gene regions affect EAE. To determine whether the immunization protocol could have an influence on clinical signs, C57BL6/J mice were immunized with a multiple antigen peptide (MAP) containing eight pMOG 35–55branches synthesized directly onto a lysine core, myelin oligodendrocyte glycoprotein 35–55–multiple antigen peptide (MOG 35–55–MAP), in complete Freund's adjuvant (CFA). In most of the mice, clinical onset (marked weakness) occurred approximately at day 15. All mice injected with MOG 35–55–MAP had more severe symptoms than those injected with pMOG 35–55, which developed no leg paralysis. All MOG 35–55–MAP-immunized mice developed EAE symptoms, but 50% had primary-progressive EAE, while the other 50% had relapsing–remitting disease. Leukocyte infiltrations, associated with increased glial fibrillary acidic protein (GFAP) expression by reactive astrocytes, were observed around the lateral ventricles and blood vessels in the brain. Significant positive correlations were established between anti-MOG 35–55antibody levels and clinical scores or GFAP positivity in the spinal cord. The heterogeneity of EAE progression, observed in these genetically identical individuals, suggests that the environment rather than the genetics plays a role. This observation is highly pertinent as it corresponds to what is seen in clinical MS.