Experimental Autoimmune Encephalomyelitis

Abstract

Experimental autoimmune encephalomyelitis (EAE) is a well-characterized animal model of multiple sclerosis (MS), a common inflammatory demyelinating disease of the central nervous system (CNS). EAE is induced in susceptible animal species by immunization with myelin proteins or their immunodominant peptides in adjuvant substances, which facilitate the initiation of immune responses. Antigen-presenting cells (APCs) prime autoreactive CD4+ T cells to react against myelin components and migrate from the lymph nodes draining the immunization site, to the blood stream, and to the CNS through the blood--brain barrier. In the CNS, myelin-reactive T cells are reactivated by local APC, such as microglia, which present myelin peptides to them. Antigen recognition in the CNS leads to the expansion of myelin-reactive T cells, which produce inflammatory molecules such as cytokines and chemokines and initiate an inflammatory cascade. Other inflammatory cells, such as macrophages and B cells, are recruited to the CNS and contribute to damage to central myelin by direct attack and myelin ``stripping'' (by macrophages), the production of inflammatory cytokines, reactive oxygen species and nitric oxide, the production of antimyelin antibodies, and the deposition of complement. Immune mechanisms of EAE support the concept that MS is an immune-mediated disease initiated by autoreactive T cells. Adoptive-transfer EAE, in which immune cells from mice with EAE are transferred to healthy recipients, directly demonstrated for the first time the role of myelin-reactive CD4+ T cells in autoimmune demyelination. Other evidence for the involvement of immune mechanisms in the pathogenesis of MS include the presence of perivenular T and B lymphocytes in MS lesions, the responsiveness of MS patients to immunomodulatory and immunosuppressive treatments, and the contribution of genes of the immune response to disease susceptibility.