Contribution of cd4+ virus-specific Vs. autoimmune t cell responses to the induction and chronic stages of theiler's virus-induced demyelinating disease

Stephen D Miller*, W. C. Pao, J. G. Pope, C. L. Vanderlual, W. J. Karous

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Theiler's murine encephalomyelitis viruses {TMEV) are endemic enteric pathogens of mice and can establish persistent central nervous system (CMS) infection which serves as a highly relevant model of multiple sclerosis (MS). Infection of susceptible mouse strains leads to a chronic, progressive inflammatory demyelinating disease of the CMS which onsets approximately 2535 days post-infection and is characterized clinically by an abnormal gait and progressive spastic hind limb paralysis and histologically by parenchymal and perivascular mononuclear cell infiltration and demyelination of CMS white matter tracts. Disease onset is initiated by CNS-filtrating, virus-specific CD4+ T cells in the apparent absence of neuroantigen-specific autoimmune responses as supported by the observation of: a) activated TMEV-specific T cells in the CMS of infected mice; b) accelerated disease onset in recipients of TMEV-specific Th1 lines; and c) dramatically reduced disease incidence in mice tolerized with intact TMEV virions prior to infection. Infected SJL/J mice fail to exhibit peripheral or CNS T cell responses to the immunodominant epitopes on MBP and PLP within the first 40 days post-infection. However, 3-4 weeks after clinical onset, T cell reactivity to the immunodominant PLP139-151 epitope develops and by 5-6 months PI T cell and antibody responses to multiple neuroepitopes are observed. Preliminary evidence suggests that myelin-specific tolerance of mice with established chronic disease has some ameliorating effects on disease progression. Thus, chronic disease appears to be mediated in part by CD4+ T cells specific for both TMEV and self myelin antigens.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number6
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Contribution of cd4+ virus-specific Vs. autoimmune t cell responses to the induction and chronic stages of theiler's virus-induced demyelinating disease'. Together they form a unique fingerprint.

Cite this