The effector phase consists of multiple stages: (1) migration of activated myelin-specific T cells to the CNS, which involves extravasation of the T cells across the tight endothelial junctions comprising the blood-brain barrier (2) elaboration of chemokines and cytokines by the myelin-specific T cells, which induce the influx of peripheral mononuclear phagocytes into the CNS parenchyma (3) activation of peripheral monocytes/macrophages and CNS-resident microglial cells by T H cell–derived cytokines and (4) demyelination of CNS axonal tracts by the phagocytic activity of activated mononuclear cells and by the inflammatory and cytotoxic effects of cytokines (e.g., IFN- γ, LT/TNF-β, IL-17, TNF- α, and NO) released from activated CD4 + T cells and monocytes. The induction phase of the disease involves the priming of myelin epitope–specific CD4 + T cells following immunization with myelin proteins or peptides in complete Freund's adjuvant (CFA). In C57BL/6 (H-2 b) mice, the disease displays a chronic-progressive clinical course, while in other mouse strains, such as PL/J (H-2 u) and B10.PL (H-2 u), the disease is normally acute and self-limiting, and is not characterized by clinical relapses.Īctively induced EAE consists of an induction phase and an effector phase. In the SJL (H-2 s) mouse, the disease is characterized by a relapsing-remitting course of paralysis, which allows assessment of the efficacy of various immunoregulatory strategies in a progressive autoimmune disease setting.
EAE provides a powerful model for the study of the pathogenesis and immune regulation of CD4 + T H1/T H17–mediated tissue damage and is generally considered to be a relevant model for the human immune-mediated demyelinating disease multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) is a CD4 + T cell–mediated autoimmune disease characterized by perivascular CD4 + T cell and mononuclear cell inflammation and subsequent primary demyelination of axonal tracks in the central nervous system (CNS), leading to progressive hind-limb paralysis.
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