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Persistent infection with Theiler's virus leads to CNS autoimmunity via epitope spreading

Persistent infection with Theiler's virus leads to CNS autoimmunity via epitope spreading Multiple sclerosis (MS) is a T cell-mediated autoimmune demyelinating disease1, which may be initiated by a virus infection2. Theiler's murine encephalomyelitis virus (TMEV), a natural mouse pathogen, is a picornavirus that induces a chronic, CD4+ T cell-mediated demyelinating disease with a clinical course and histopathology similar to that of chronic progressive MS (ref. 3). Demyelination in TMEV-infected mice is initiated by a mononu-clear inflammatory response mediated by virus-specific CD4+ T cells targeting virus, which chronically persists in the CNS (ref. 4–6). We show that beginning 3–4 weeks after disease onset, T-cell responses to multiple myelin autoepitopes arise in an ordered progression and may play a pathologic role in chronic disease. Kinetic and functional studies show that T-cell responses to the immunodominant myelin proteolipid protein epitope (PLP139–151) did not arise because of cross-reactivity between TMEV and self epitopes (that is, molecular mimicry)7, 8, but because of de novo priming of self-reactive T cells to sequestered autoantigens released secondary to virus-specific T cell-mediated demyelination (that is, epitope spreading)9, 10. Epitope spreading is an important alternate mechanism to explain the etiology of virus-induced organ-specific autoimmune diseases. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Medicine Springer Journals

Persistent infection with Theiler's virus leads to CNS autoimmunity via epitope spreading

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References (24)

Publisher
Springer Journals
Copyright
Copyright © 1997 by Nature Publishing Group
Subject
Biomedicine; Biomedicine, general; Cancer Research; Metabolic Diseases; Infectious Diseases; Molecular Medicine; Neurosciences
ISSN
1078-8956
eISSN
1546-170X
DOI
10.1038/nm1097-1133
Publisher site
See Article on Publisher Site

Abstract

Multiple sclerosis (MS) is a T cell-mediated autoimmune demyelinating disease1, which may be initiated by a virus infection2. Theiler's murine encephalomyelitis virus (TMEV), a natural mouse pathogen, is a picornavirus that induces a chronic, CD4+ T cell-mediated demyelinating disease with a clinical course and histopathology similar to that of chronic progressive MS (ref. 3). Demyelination in TMEV-infected mice is initiated by a mononu-clear inflammatory response mediated by virus-specific CD4+ T cells targeting virus, which chronically persists in the CNS (ref. 4–6). We show that beginning 3–4 weeks after disease onset, T-cell responses to multiple myelin autoepitopes arise in an ordered progression and may play a pathologic role in chronic disease. Kinetic and functional studies show that T-cell responses to the immunodominant myelin proteolipid protein epitope (PLP139–151) did not arise because of cross-reactivity between TMEV and self epitopes (that is, molecular mimicry)7, 8, but because of de novo priming of self-reactive T cells to sequestered autoantigens released secondary to virus-specific T cell-mediated demyelination (that is, epitope spreading)9, 10. Epitope spreading is an important alternate mechanism to explain the etiology of virus-induced organ-specific autoimmune diseases.

Journal

Nature Medicine – Springer Journals

Published: Oct 1, 1997

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