Epitope spreading is not required for relapses in experimental autoimmune encephalomyelitis

Richard E. Jones, Dennis Bourdette, Nicole Moes, Arthur Vandenbark, Alex Zamora, Halina Offner

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

The sequential emergence of specific T lymphocyte-mediated immune reactivity directed against multiple distinct myelin epitopes (epitope spreading) has been associated with clinical relapses in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Based on this association, an appealing and plausible model for immune-mediated progression of the advancing clinical course in MS and EAE has been proposed in which epitope spreading is the cause of clinical relapses in T cell-mediated CNS inflammatory diseases. However, the observed association between epitope spreading and disease progression is not universal, and absolute requirements for epitope spreading in progressive EAE have not been tested in the absence of multiple T cell specificities, because most prior studies have been conducted in immunocompetent mouse strains that possessed broad TCR repertoires. Consequently, the precise nature of a causal relationship between epitope spreading and disease progression remains uncertain. To determine whether relapsing or progressive EAE can occur in the absence of epitope spreading, we evaluated the course of disease in mice which possessed only a single myelin-specific TCR. These mice (transgenic/SCID +/+) exhibited a progressive and sometimes remitting/relapsing disease course in the absence of immune reactivity to multiple, spreading myelin epitopes. The results provide direct experimental evidence relevant to discussions on the mechanisms of disease progression in MS and EAE.

Original languageEnglish (US)
Pages (from-to)1690-1698
Number of pages9
JournalJournal of Immunology
Volume170
Issue number4
DOIs
StatePublished - Feb 15 2003

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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