Modeling the heterogeneity of multiple sclerosis in animals

Abstract

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system 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 central nervous system 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.

Lymphocryptovirus Infection of Nonhuman Primate B Cells Converts Destructive into Productive Processing of the Pathogenic CD8 T Cell Epitope in Myelin Oligodendrocyte Glycoprotein

“…Briefly, 50 ml of MNC lysate (200 mg protein/ml) was incubated with CH reaction buffer and CH R-AFC substrate for 24 h at 37˚C. Color reaction was measured with the VICTOR 3 Multilabel Counter model 1420 (PerkinElmer) at excitation 405 nm/emission 535 nm. Data are expressed as arbitrary counts.…”

“…The total mixture was incubated for 24 h at 37˚C, and fluorescence was measured with the VICTOR 3 Multilabel Counter model 1420 (PerkinElmer) at an excitation wavelength of 355 nm and an emission wavelength of 460 nm. As positive control, 5 mU/ml human CatG (Sigma-Aldrich) was used.…”

“…T cells have a core pathogenic role in the EAE model, but it is unclear whether data obtained in inbred/specific pathogen-free rodents can be directly translated to the pathogen-educated immune system of outbred primates (3). In recent years, we investigated the distinct pathogenic roles of autoaggressive CD4 + and CD8 + T cells in nonhuman primate models of MS: EAE in the small-bodied common marmoset (Callithrix jacchus) and the larger-bodied rhesus macaque (Macaca mulatta).…”

Current Developments In Mri For Assessing Rodent Models of Multiple Sclerosis

“…There are three types of adjuvants included in immunization protocols used to induce EAE: Quil Adjuvant (A), complete Freud's adjuvant (CFA) and pertussis toxin, [50,51]. A mild EAE model with a relapsing remitting (RR) cycle followed by a complete recovery period can be induced using MOG 35--55 (myelin oligodendrocyte glycoprotein peptide sequence 35--55) and Quil A, which acts once at the site of immunisation [52].…”

“…Various EAE rodent models of MS have increased our collective understanding of the immunopathology and neurodegenerative aspects of MS, which led to successful development of three currently marketed therapeutic drugs, namely, glatiramer acetate, mitoxantrone and natalizumab, all which have been approved by the FDA (The US Food and Drug Administration) for clinical treatment [45,51]. A limitation of EAE--rodent models is that they do not adequately mimic the auto immune factors that contribute to MS disease pathology [47].…”