CD8+ T cells directed against a viral peptide contribute to loss of motor function by disrupting axonal transport in a viral model of fulminant demyelination

Charles L Howe, Daren Ure, Jaimie D. Adelson, Reghann LaFrance-Corey, Aaron J. Johnson, Moses Rodriguez

Research output: Contribution to journalArticle

31 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)13-21
Number of pages9
JournalJournal of Neuroimmunology
Volume188
Issue number1-2
DOIs
StatePublished - Aug 2007

Fingerprint

Axonal Transport
Demyelinating Diseases
Axons
T-Lymphocytes
Peptides
Wounds and Injuries
Multiple Sclerosis
Theilovirus
Antiviral Agents
Spinal Cord
Infection
Population

Keywords

  • Axon injury
  • Cytotoxic T cells
  • Interferon-gamma
  • MHC Class I
  • Multiple sclerosis
  • Retrograde transport

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

CD8+ T cells directed against a viral peptide contribute to loss of motor function by disrupting axonal transport in a viral model of fulminant demyelination. / Howe, Charles L; Ure, Daren; Adelson, Jaimie D.; LaFrance-Corey, Reghann; Johnson, Aaron J.; Rodriguez, Moses.

In: Journal of Neuroimmunology, Vol. 188, No. 1-2, 08.2007, p. 13-21.

Research output: Contribution to journalArticle

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