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CD40-CD40 ligand interactions in experimental allergic encephalomyelitis and multiple sclerosis
K Gerritse1, J D Laman, R J Noelle
1Division of Immunological and Infectious Diseases, TNO Prevention and Health, Leiden, The Netherlands.
Summary
Blocking CD40-CD40 ligand interactions shows promise for treating multiple sclerosis (MS). This approach prevented and reduced disease severity in experimental allergic encephalomyelitis (EAE), an MS model.
Area of Science:
- Immunology
- Neuroscience
- Cell Biology
Background:
- Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
- CD40-CD40 ligand (CD40L) interactions play a role in immune responses and inflammation.
Purpose of the Study:
- To investigate the role of CD40-CD40L interactions in MS and experimental allergic encephalomyelitis (EAE).
- To evaluate the therapeutic potential of blocking CD40-CD40L interactions in EAE.
Main Methods:
- Analysis of brain tissue from MS patients and EAE models for CD40 and CD40L expression.
- Induction of EAE in mice using proteolipid-peptide immunization.
- Treatment of EAE mice with anti-CD40L monoclonal antibody before disease onset and after disease onset.
Main Results:
- CD40L-expressing helper T cells were found in active MS lesions, co-localized with CD40-bearing cells (monocytes, macrophages, microglial cells).
- Anti-CD40L antibody treatment completely prevented EAE development.
- Administration of anti-CD40L antibody after disease onset significantly reduced disease severity.
Conclusions:
- CD40-CD40L interactions are implicated in the pathogenesis of MS and EAE.
- Blockade of CD40-CD40L interactions represents a potential therapeutic strategy for active MS.