Abstract
Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), a multiple sclerosis (MS) model, is a central nervous system (CNS) demyelinating disease characterized by early peripheral T cell responses to virus epitopes which spreads to myelin epitopes during chronic disease. We show that CD4+ T cells isolated from the spinal cords of chronically infected SJL mice proliferate and secrete pro-inflammatory cytokines upon in vitro challenge with both TMEV epitopes and proteolipid protein (PLP139-151). Importantly, myelin-specific tolerance induced by intravenous administration of MP4, a fusion of the myelin proteins myelin basic protein (MBP) and PLP, to SJL mice with ongoing TMEV-IDD attenuated disease progression and resulted in significantly less demyelination and decreased inflammatory cell infiltration in the CNS. Paradoxically, peptide-specific splenic T cell proliferative and IFN-γ responses were enhanced in the tolerized mice. Collectively, these results indicate that myelin-specific T cell responses contribute to chronic disease progression in this virus-induced model of MS, and suggest caution in the use of antigen-specific tolerance for treatment of ongoing autoimmune disease.
Original language | English (US) |
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Pages (from-to) | 18-29 |
Number of pages | 12 |
Journal | Journal of Neuroimmunology |
Volume | 123 |
Issue number | 1-2 |
DOIs | |
State | Published - 2002 |
Keywords
- Autoimmune disease
- Epitope spreading
- Immune regulation
- Proteolipid protein
- Theiler's virus
ASJC Scopus subject areas
- Clinical Neurology
- Neurology
- Immunology and Allergy
- Immunology