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Updated: Jun 8, 2026
Modeling Multiple Sclerosis in the Two Sexes: MOG35-55-Induced Experimental Autoimmune Encephalomyelitis
Published on: October 13, 2023
Gender differences in CNS autoimmunity induced by mimicry epitope for PLP 139-151 in SJL mice
Chandirasegaran Massilamany1, Sivasubramani Thulasingam, David Steffen
1School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, United States.
Abstract:
Development of multiple sclerosis (MS) is more prevalent in females than in males, but the underlying mechanisms are not clear. Microbial infections have been suspected as triggers of MS and it is not known whether gender differences in reactivity to environmental antigens contribute to the disease pathogenesis. We demonstrated that ACA 83-95, a mimicry epitope from Acanthamoeba castellanii for proteolipid protein (PLP) 139-151, induces clinical signs of encephalomyelitis in both male and female SJL mice. Conversely ACA 83-95-induced effector cells from males fail to induce disease in female mice. Although we found no gender differences in the frequencies of antigen-specific cells including cytokine production, PLP-specific cells induced with ACA 83-95 differed in T cell receptor vβ usage from those induced with PLP 139-151. The data suggest that cross-reactive T cell expansion occurs similarly in both males and females, but their disease-inducing ability is influenced by gender.
Insights
Gender influences the disease-inducing ability of T cells in experimental autoimmune encephalomyelitis, despite similar cross-reactive T cell expansion in male and female mice. This finding offers insights into multiple sclerosis pathogenesis.
Area of Science:
- Immunology
- Neuroscience
- Microbiology
Background:
- Multiple sclerosis (MS) exhibits higher prevalence in females, yet the underlying reasons remain unclear.
- Microbial infections are implicated as potential triggers for MS.
- The role of gender-specific immune responses to environmental antigens in MS pathogenesis is not well understood.
Purpose of the Study:
- To investigate the influence of gender on the development of experimental autoimmune encephalomyelitis (EAE) induced by a microbial epitope mimicking a myelin antigen.
- To explore gender-based differences in T cell responses following exposure to cross-reactive antigens.
Main Methods:
- Induction of encephalomyelitis in male and female SJL mice using ACA 83-95, an epitope from Acanthamoeba castellanii mimicking proteolipid protein (PLP) 139-151.
- Assessment of disease induction by ACA 83-95-primed effector cells transferred between genders.
- Analysis of antigen-specific T cell frequencies, cytokine production, and T cell receptor (TCR) vβ usage.
Main Results:
- ACA 83-95 induced clinical signs of encephalomyelitis in both male and female mice.
- Effector cells from male mice, primed with ACA 83-95, failed to induce disease in female recipients.
- No significant gender differences were observed in the frequencies of antigen-specific cells or cytokine production.
- PLP-specific T cells induced by ACA 83-95 exhibited distinct TCR vβ usage compared to those induced by PLP 139-151.
Conclusions:
- Cross-reactive T cell expansion occurs similarly in both male and female mice.
- Gender significantly influences the disease-inducing capacity of effector T cells in this model of MS.
- These findings highlight the complex interplay between gender, microbial triggers, and autoimmune responses in neuroinflammation.
