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Age dependence of clinical and pathological manifestations of autoimmune demyelination. Implications for multiple
M E Smith1, N L Eller, H F McFarland
1Neuroimmunology Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. BS161v@nih.gov
Abstract:
A prominent feature of the clinical spectrum of multiple sclerosis (MS) is its high incidence of onset in the third decade of life and the relative rarity of clinical manifestations during childhood and adolescence, features suggestive of age-related restriction of clinical expression. Experimental allergic encephalomyelitis (EAE), a model of central nervous system (CNS) autoimmune demyelination with many similarities to MS, has a uniform rapid onset and a high incidence of clinical and pathological disease in adult (mature) animals. Like MS, EAE is most commonly seen and studied in female adults. In this study, age-related resistance to clinical EAE has been examined with the adoptive transfer model of EAE in SJL mice that received myelin basic protein-sensitized cells from animals 10 days (sucklings) to 12 weeks (young adults) of age. A variable delay before expression of clinical EAE was observed between the different age groups. The preclinical period was longest in the younger (<14 days of age) animals, and shortest in animals 6 to 8 weeks old at time of transfer. Young animals initially resistant to EAE eventually expressed well-developed clinical signs by 6 to 7 weeks of age. This was followed by a remitting, relapsing clinical course. For each age at time of sensitization, increased susceptibility of females compared to males was observed. Examination of the CNS of younger animal groups during the preclinical period showed lesions of acute EAE. Older age groups developed onset of signs coincident with acute CNS lesions. This age-related resistance to clinical EAE in developing mice is reminiscent of an age-related characteristic of MS previously difficult to study in vivo. The associated subclinical CNS pathology and age-related immune functions found in young animals may be relevant to the increasing clinical expression of MS with maturation, and may allow study of factors associated with the known occasional poor correlation of CNS inflammation and demyelination and clinical changes in this disease.
Insights
Young mice show delayed clinical signs of experimental allergic encephalomyelitis (EAE), a multiple sclerosis (MS) model, suggesting age-related immune resistance. This resistance in developing mice offers insights into MS onset and progression.
Area of Science:
- Neuroimmunology
- Demyelinating Diseases
- Developmental Immunology
Background:
- Multiple sclerosis (MS) typically manifests in early adulthood, with rare childhood or adolescent onset.
- Experimental allergic encephalomyelitis (EAE) in adult animals closely models MS but shows rapid onset, unlike MS's age-restricted clinical expression.
Purpose of the Study:
- To investigate age-related resistance to clinical EAE using an adoptive transfer model in mice.
- To understand how age influences the onset and severity of autoimmune demyelination.
Main Methods:
- Adoptive transfer of myelin basic protein-sensitized cells into SJL mice of varying ages (10 days to 12 weeks).
- Monitoring for clinical signs of EAE and examining central nervous system (CNS) pathology.
- Assessing sex-based differences in disease susceptibility.
Main Results:
- A variable delay in EAE onset was observed, with younger animals (<14 days) exhibiting the longest preclinical period.
- Young animals eventually developed clinical EAE with a relapsing-remitting course, showing acute CNS lesions.
- Females consistently showed increased susceptibility to EAE compared to males across all age groups.
Conclusions:
- Developing mice demonstrate age-related resistance to clinical EAE, mirroring MS's clinical presentation.
- Subclinical pathology and age-dependent immune function in young animals may explain delayed MS onset.
- This model provides a platform to study factors influencing MS clinical expression and CNS inflammation correlation.