Spontaneous CNS remyelination in β2 microglobulin-deficient mice following virus-induced demyelination

David J. Miller, Cynthia Rivera-Quiñones, M. Kariuki Njenga, Julian Leibowitz, Moses Rodriguez

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Animal models with selective genetic immunodeficiencies are useful tools to identify pathogenic mechanisms of disease. Resistant (C57BL/6F 129/J) (H- 2b) mice are rendered susceptible to Theiler's murine encephalomyelitis virus-induced demyelination by genetic disruption of the β2 microglobulin gene [β2m(-/-)]. The absence of β2m prevents the expression of major histocompatibility complex class I molecules and normal levels of functional CD8+ T cells. We tested whether genetic depletion of β2m would permit CNS remyelination after chronic demyelination induced by the Daniel's strain of Theiler's virus. In contrast to the minimal spontaneous remyelination observed in SJL/J mice after infection with the Daniel's strain of Theiler's virus, chronically infected β2m(-/-) mice showed extensive and progressive spontaneous CNS remyelination at 6, 12, and 18 months after infection. Spontaneous remyelination by both oligodendrocytes and Schwann cells occurred despite the presence of persistent virus antigen and RNA, but was associated with diminished virus-specific humoral and delayed-type hypersensitivity responses. These experiments support the hypothesis that the immune response inhibits myelin regeneration after virus-induced CNS demyelination.

Original languageEnglish (US)
Pages (from-to)8345-8352
Number of pages8
JournalJournal of Neuroscience
Volume15
Issue number12
StatePublished - Dec 1 1995

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Keywords

  • CD8 T cell
  • MHC class I
  • Schwann cell
  • Theiler's virus
  • delayed- type hypersensitivity
  • myelin
  • oligodendrocyte

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Miller, D. J., Rivera-Quiñones, C., Njenga, M. K., Leibowitz, J., & Rodriguez, M. (1995). Spontaneous CNS remyelination in β2 microglobulin-deficient mice following virus-induced demyelination. Journal of Neuroscience, 15(12), 8345-8352.