Age-Dependent Effects of Transgenic 2D2 Mice Used to Induce Passive Experimental Autoimmune Encephalomyelitis in
James M Nichols1, Barbara L F Kaplan2
1Department of Comparative Biomedical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi, USA.
Introduction:
Multiple sclerosis (MS) is a neurodegenerative autoimmune disease that worsens with age. Here, we examined the influence of age on passive experimental autoimmune encephalomyelitis (P-EAE), a model to study MS, using young and mature adult 2D2 transgenic donor mice to induce pathology in WT C57BL6/J mice.
Methods:
Lymphocytes from young adult (i.e., 10-week-old) or mature adult (i.e., 6-month-old) transgenic donor mice were characterized by flow cytometry prior to injection of cultured leukocytes into adult female WT recipient mice, with a special focus on transgenic T cell phenotypes.
Results:
Our findings show age-dependent changes in memory T cell phenotypes correlated with more severe clinical and histological disease when donor cells originated from young as compared to mature adult mice.
Conclusion:
Not only do these results demonstrate that the age of the 2D2 transgenic donor mice is critical in establishing P-EAE, but the differential effects might also identify age-dependent factors that contribute to EAE and perhaps MS.
Insights
Donor mouse age significantly impacts multiple sclerosis (MS) model severity. Young donor mice led to worse disease, suggesting age-related factors influence autoimmune responses in experimental autoimmune encephalomyelitis (EAE).
Area of Science:
- Immunology
- Neuroscience
- Aging Research
Background:
- Multiple sclerosis (MS) is a progressive neurodegenerative autoimmune disorder.
- Age is a known factor influencing MS progression and severity.
- Experimental autoimmune encephalomyelitis (EAE) serves as a key animal model for studying MS.
Purpose of the Study:
- To investigate the influence of donor mouse age on the development and severity of passive experimental autoimmune encephalomyelitis (P-EAE).
- To identify age-dependent immunological factors contributing to autoimmune neuroinflammation.
Main Methods:
- Utilized young (10-week-old) and mature adult (6-month-old) 2D2 transgenic mice as T cell donors.
- Characterized donor lymphocyte phenotypes using flow cytometry.
- Induced P-EAE in WT C57BL6/J recipient mice by adoptive transfer of cultured donor leukocytes.
Main Results:
- Donor mouse age demonstrably influenced P-EAE outcomes.
- T cell phenotypes exhibited age-dependent variations.
- Younger donor mice resulted in more severe clinical and histological disease compared to mature adult donors.
Conclusions:
- The age of the donor mice is a critical determinant in establishing P-EAE.
- Age-related differences in donor immune cells contribute to varying disease severity.
- Findings may elucidate age-dependent mechanisms relevant to EAE and MS pathogenesis.
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