Allergic Encephalomyelitis in Common Marmosets: Pathogenesis of a Multiple Sclerosis-like Lesion
Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system that has been extensively studied as a model for the human demyelinating disease multiple sclerosis (MS). Here we describe the characteristics of a novel form of EAE developed in a nonhuman primate. In Callithrix jacchus marmosets (C. jacchus), immunization with whole brain white matter induces a primary demyelinating disease with a relapsing-remitting chronic course, closely resembling human MS. In these animals, the MS-like lesion results from a complex immune response requiring both disease-inducing T lymphocytes and pathogenic antibody. T lymphocytes reactive against myelin basic protein are capable of mediating the inflammatory component of marmoset EAE. Demyelination, on the other hand, is antibody mediated. The quantitatively minor myelin protein myelin oligodendrocyte glycoprotein (MOG) is an important antigen in this system, as immunization against MOG, or passive transfer of anti-MOG antibodies, reproduces the core features of the disease induced with whole white matter. Advantages of the C. jacchus model of EAE for the study of MS include the clinical and pathologic similarity between the two conditions, the natural bone marrow chimerism in C. jacchus permitting adoptive transfer of T lymphocytes between siblings, and the similarity of immune and nervous system genes and proteins between human and nonhuman primates. A diverse immune response to multiple myelin antigens appears to be responsible for the MS-like lesion in C. jacchus, a finding that parallels emerging concepts of the pathogenesis of human MS.