Antibody association with a novel model for primary progressive multiple sclerosis: induction of relapsing-remitting and progressive forms of EAE in H2s mouse strains
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Updated: Oct 15, 2026
Induction of Experimental Autoimmune Encephalomyelitis in Mice and Evaluation of the Disease-dependent Distribution of Immune Cells in Various Tissues
Published on: May 8, 2016
I Tsunoda1, L Q Kuang, D J Theil
1Department of Neurology, University of Utah School of Medicine, Salt Lake City 84132, USA.
Abstract:
Multiple sclerosis (MS) can be divided into 4 clinical forms: relapsing-remitting (RR), primary progressive (PP), secondary progressive (SP), and progressive relapsing (PR). Since PP-MS is notably different from the other forms of MS, both clinically and pathologically, the question arises whether PP-MS is immunologically similar to the other forms. The pathogenesis of the PP-MS remains unclear, partly due to a lack of highly relevant animal models. Using an encephalitogenic peptide from myelin oligodendrocyte glycoprotein (MOG)92-106, we have established animal models that mimic different forms of MS in 2 strains of H-2s mice, SJL/J and A.SW. We induced experimental allergic encephalomyelitis (EAE) using MOG92-106 in the presence or absence of supplemental Bordetella pertussis (BP). Although, SJL/J mice developed RR-EAE whether BP was given or not, A.SW mice developed PP-EAE without BP and SP-EAE with BP. Histologically, SJL/J mice developed mild demyelinating disease with T cell infiltration, while A.SW mice developed large areas of plaque-like demyelination with immunoglobulin deposition and neutrophil infiltration, but with minimal T cell infiltration. In A.SW mice without BP, high titer serum anti-MOG antibody was detected and the anti-MOG IgG2a/IgG1 ratio correlated with survival times of mice. We hypothesized that, in A.SW mice, a Th2 response favors production of myelinotoxic antibodies, leading to progressive forms with early death. Our new models indicate that a single encephalitogen could induce either RR-, PP-, or SP- forms of demyelinating disease in hosts with immunologically different humoral immune responses.
Insights
This study developed new animal models for multiple sclerosis (MS) by using a myelin oligodendrocyte glycoprotein peptide. Different forms of MS, including relapsing-remitting, primary progressive, and secondary progressive, were induced, revealing distinct immunological responses.
Area of Science:
- Neuroimmunology
- Demyelinating Diseases
- Autoimmunity
Background:
- Multiple sclerosis (MS) presents with distinct clinical forms: relapsing-remitting (RR), primary progressive (PP), secondary progressive (SP), and progressive relapsing (PR).
- Primary progressive MS (PP-MS) exhibits unique clinical and pathological characteristics, raising questions about its immunological similarity to other MS forms.
- The pathogenesis of PP-MS is not fully understood, partly due to the absence of highly relevant animal models.
Purpose of the Study:
- To establish novel animal models that mimic different clinical forms of MS.
- To investigate the immunological mechanisms underlying the distinct forms of experimental allergic encephalomyelitis (EAE).
- To explore the role of humoral immune responses in the development of progressive demyelinating diseases.
Main Methods:
- Induction of experimental allergic encephalomyelitis (EAE) in SJL/J and A.SW mice using an encephalitogenic peptide (MOG92-106) from myelin oligodendrocyte glycoprotein.
- Administration of Bordetella pertussis (BP) in conjunction with the encephalitogenic peptide to modulate the immune response.
- Histological analysis of brain tissue to assess demyelination, immune cell infiltration, and immunoglobulin deposition.
- Measurement of anti-MOG antibody titers and analysis of IgG subclass ratios (IgG2a/IgG1).
Main Results:
- SJL/J mice consistently developed RR-EAE, irrespective of BP administration.
- A.SW mice developed PP-EAE in the absence of BP and SP-EAE in the presence of BP.
- Histopathology revealed mild demyelination with T cell infiltration in SJL/J mice, contrasting with extensive plaque-like demyelination, immunoglobulin deposition, and neutrophil infiltration but minimal T cell infiltration in A.SW mice.
- In A.SW mice, high anti-MOG antibody titers were detected, with the IgG2a/IgG1 ratio correlating with survival, suggesting a Th2-mediated autoimmune response driving progressive disease.
Conclusions:
- A single encephalitogenic peptide can induce different clinical forms of demyelinating disease (RR, PP, SP) depending on the host's immunological background.
- The distinct EAE forms in A.SW mice are associated with differential humoral immune responses, potentially involving myelinotoxic antibodies in progressive MS.
- These findings provide valuable insights into the immunopathogenesis of MS subtypes and offer relevant models for future research.
