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Analysis of experimental autoimmune encephalomyelitis induced in F344 rats by pertussis toxin administration
1Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan.
Abstract:
To elucidate the factor(s) accelerating the autoimmune disease processes, we induced two types of experimental autoimmune encephalomyelitis (EAE), severe and very mild, in F344 rats by immunization with myelin basic protein (MBP) plus pertussis toxin (PT) (PT+) or with MBP alone (PT-) and compared the differences between the two. Immunohistochemical examinations showed that although the nature of inflammation was essentially the same between the two groups, the proportion of Vbeta8.2(+) T cells in the CNS lesion of PT (+) rats was larger than that of PT (-) rats. Cytokine analysis by competitive PCR revealed that IL-10 mRNA in the lymphoid organ was significantly suppressed in the PT(+) group, whereas levels of IFN-gamma,TNF-alpha and TGF-beta mRNA were insignificantly different after PT administration. In addition, T cells taken from PT (+) rats proliferated well in response to MBP, while those from PT (-) rats showed a marginal response to the same antigen. However, this finding does not indicate the switching of non-encephalitogenic to encephalitogenic T cells upon PT administration because PT (-) rats contained encephalitogenic T cells and/or their precursor cells as revealed by adoptive transfer experiments. Taken together, these findings suggest that suppression of IL-10 by PT administration is the major factor contributing to the exacerbation of EAE in PT(+) rats.
Insights
Pertussis toxin (PT) exacerbates experimental autoimmune encephalomyelitis (EAE) by suppressing interleukin-10 (IL-10) production. This suppression leads to increased T cell response to myelin basic protein (MBP), worsening autoimmune disease progression.
Area of Science:
- Neuroimmunology
- Autoimmune Diseases
Background:
- Experimental autoimmune encephalomyelitis (EAE) is a model for multiple sclerosis.
- Factors accelerating autoimmune disease progression require elucidation.
Purpose of the Study:
- To identify factors that accelerate autoimmune disease processes.
- To compare EAE severity induced by myelin basic protein (MBP) with or without pertussis toxin (PT).
Main Methods:
- Induction of severe (MBP + PT) and mild (MBP alone) EAE in F344 rats.
- Immunohistochemical analysis of T cells in the central nervous system (CNS).
- Cytokine mRNA analysis using competitive PCR and T cell proliferation assays.
Main Results:
- PT(+) rats showed a higher proportion of Vbeta8.2(+) T cells in CNS lesions compared to PT(-) rats.
- IL-10 mRNA was significantly suppressed in PT(+) rats; other cytokines showed no significant difference.
- T cells from PT(+) rats exhibited enhanced proliferation to MBP.
Conclusions:
- Suppression of IL-10 by PT administration is a key factor in EAE exacerbation.
- PT enhances T cell responses to MBP without switching T cell populations.
- Findings suggest IL-10 modulation as a therapeutic target for autoimmune neuroinflammation.