Abstract
Demyelination, a pathological hallmark of multiple sclerosis, may be a necessary but not a sufficient condition for motor dysfunction associated with this disease. We favor a neurodegenerative model of multiple sclerosis and suggest that demyelination creates a permissive environment wherein the denuded axon becomes susceptible to immune-mediated injury. Unfortunately, the cellular effectors responsible for eliciting such axonal injury are currently unknown. Based on previous observations implicating cytotoxic T cells in this injury, we assessed motor function, axon dropout, and axon injury following peptide depletion of the immunodominant CD8+ antiviral T cell response in the IFNγ receptor-deficient mouse model of acute demyelination. We found that the targeted removal of this population of cytotoxic effector cells prior to infection with the Theiler's murine encephalomyelitis virus caused a substantial preservation of motor function at 45 days postinfection that was associated with preservation of retrograde axonal transport in a subpopulation of surviving axons within the spinal cord. We conclude that cytotoxic T cells may be responsible for the initiation of axon injury following demyelination.
Original language | English (US) |
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Pages (from-to) | 13-21 |
Number of pages | 9 |
Journal | Journal of neuroimmunology |
Volume | 188 |
Issue number | 1-2 |
DOIs | |
State | Published - Aug 2007 |
Keywords
- Axon injury
- Cytotoxic T cells
- Interferon-gamma
- MHC Class I
- Multiple sclerosis
- Retrograde transport
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Neurology
- Clinical Neurology