Modeling the heterogeneity of multiple sclerosis in animals

•Multiple animal models are needed to model the heterogeneous features of MS.•Individual EAE models replicate specific features of disease.•Collectively, EAE models link CD4 T, CD8 T, and B cells to disease pathogenesis.•Additional models are needed for primary and secondary progressive MS.

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS) manifested with varying clinical course, pathology, and inflammatory patterns. There are multiple animal models that reflect different aspects of this heterogeneity. Collectively, these models reveal a balance between pathogenic and regulatory CD4+ T cells, CD8+ T cells, and B cells that influences the incidence, timing, and severity of CNS autoimmunity. In this review we discuss experimental autoimmune encephalomyelitis (EAE) models that have been used to study the pathogenic and regulatory roles of these immune cells; models that recapitulate different aspects of the disease seen in patients with MS, and questions remaining for future studies.