Interference with costimulation alters disease course in Theiler's Murine Encephalomyelitis Virus-Induced Demyelinating Disease (TMEV-IDD)

Katherine L. Neville, Jeffrey A. Bluestone, Stephen D. Miller

Research output: Contribution to journalArticlepeer-review

Abstract

Theiler's virus-induced demyelinating disease is a relevant model for the autoimmune disease multiple sclerosis (MS). Approximately 30 days after intracerebral inoculation of SJL mice with TMEV, clinical disease signs arise, characterized by spastic paralysis, chronic disease progression, and mononuclear cell infiltrate into the central nervous system (CNS). While initial demyelination in TMEV-IDD is mediated by virus-specific CD4+ T cells, 50-55 days post infection, reactivity to a myelin antigen, proteolipid protein epitope 139-151, can be detected in TMEV infected mice, demonstrating an autoimmune component in this virally induced disease. Administration of molecules which interfere with proper T cell costimulation such as aB7-1, aB7-2, or CTLA-4Ig have been shown to affect disease progression in certain experimental autoimmune diseases. Treatment of TMEV infected SJL mice with costimulatory antagonists at the time of infection indicates aB7-1, aB7-1/aB7-2 in combination, and CTLA-4Ig increase disease severity and delayed type hypersensitivity (DTH) responses to viral and myelin antigens. However, the same treatment begun 25 or 45 days post infection indicates CTLA-4Ig treatment may decrease disease severity, and subsequently decrease DTH reactivity to viral and myelin antigens. This work indicates that costimulatory molecules play a critical role in the progression of viral disease and can affect the progression of TMEV-IDD into an autoimmune disease.

Original languageEnglish (US)
Pages (from-to)A1100
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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