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Induction of relapsing paralysis in experimental autoimmune encephalomyelitis by bacterial superantigen
1Department of Neurology, Stanford University School of Medicine, California 94305.
Abstract:
The role of infection in the pathogenesis of clinical relapses that occur in most autoimmune diseases, including multiple sclerosis, remains to be established. Experimental autoimmune encephalomyelitis (EAE) serves as a model for multiple sclerosis, with episodes of relapsing paralysis. In certain strains of mice, T-lymphocytes expressing the V beta 8 T-cell receptor (TCR) engage the amino-terminal epitope Ac1-11 of myelin basic protein, leading to EAE. The bacterial superantigen staphylococcal enterotoxin B (SEB) activates V beta 8-expressing T cells. Here we show that after immunization with Ac1-11, or after transfer of encephalitogenic T-cell lines or clones reactive to Ac1-11, SEB induces exacerbation or relapses of paralytic disease in mice that are in clinical remission following an initial episode of paralysis, and triggers paralysis in mice with subclinical disease. Tumour necrosis factor has a critical role in the mechanism underlying SEB-induced exacerbation of disease, because anti-tumour necrosis factor antibody given in vivo delays the onset of paralysis triggered by SEB. On reactivation of autoaggressive cells through their T-cell receptor, superantigens may induce clinical relapses of autoimmune disease.
Insights
Bacterial superantigens like staphylococcal enterotoxin B (SEB) can trigger relapses in autoimmune diseases, such as multiple sclerosis. This occurs by reactivating T-cells, highlighting infection
Area of Science:
- Neuroimmunology
- Autoimmune Diseases
- Infectious Disease
Background:
- The role of infection in autoimmune disease relapses, including multiple sclerosis, is not fully understood.
- Experimental autoimmune encephalomyelitis (EAE) is a mouse model for multiple sclerosis characterized by relapsing paralysis.
- T-cell receptor (TCR) V beta 8+ T-cells interacting with myelin basic protein's Ac1-11 epitope induce EAE in specific mouse strains.
Purpose of the Study:
- To investigate the impact of bacterial superantigens on autoimmune disease relapses.
- To determine if superantigens can induce or exacerbate paralytic disease in a multiple sclerosis model.
Main Methods:
- Utilized the experimental autoimmune encephalomyelitis (EAE) mouse model.
- Administered staphylococcal enterotoxin B (SEB), a bacterial superantigen, to mice with varying disease states (remission, subclinical).
- Investigated the role of tumor necrosis factor (TNF) by using anti-TNF antibodies.
Main Results:
- SEB administration exacerbated paralytic disease in mice in clinical remission and triggered paralysis in mice with subclinical EAE.
- Anti-TNF antibody treatment delayed the onset of SEB-induced paralysis, indicating TNF's critical role.
- Superantigen-mediated reactivation of autoaggressive T-cells can induce clinical relapses in autoimmune conditions.
Conclusions:
- Bacterial superantigens can precipitate clinical relapses in autoimmune diseases by reactivating autoreactive T-cells.
- Tumor necrosis factor plays a key role in the exacerbation of autoimmune disease triggered by superantigens.
- This study provides insights into infection-triggered relapses in autoimmune disorders like multiple sclerosis.