CTLA-4 downregulates epitope spreading and mediates remission in relapsing experimental autoimmune encephalomyelitis

Nitin J. Karandikar, Todd N. Eagar, Carol L. Vanderlugt, Jeffrey A. Bluestone, Stephen D. Miller

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

During the progression of relapsing experimental autoimmune encephalomyelitis (R-EAE), in SJL mice, disease relapses are mediated by T cells specific for non-cross-reactive myelin epitopes, a process termed 'epitope spreading'. CTLA-4, a negative regulator of T cell function modulates R-EAE, in that CTLA-4 blockade exacerbates clinical R-EAE. Herein, we show that CTLA-4-mediated signaling negatively regulates the dynamic spread of autoreactive T cell responses during the course of autoimmune disease. Anti-CTLA-4 mAb, administration at various points during the progression of R-EAE exacerbated subsequent clinical disease and enhanced T cell reactivity to both inducing and relapse-associated epitopes. In addition, CTLA-4 blockade during acute disease inhibited clinical remission. Thus, CTLA-4-mediated events are critical for intrinsic regulation of epitope spreading during autoimmune disease. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)173-180
Number of pages8
JournalJournal of Neuroimmunology
Volume109
Issue number2
DOIs
StatePublished - Sep 22 2000

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Keywords

  • Autoimmunity
  • Costimulation
  • CTLA-4
  • EAE
  • Epitope Spreading

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Clinical Neurology
  • Neurology

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