Blockade of CD28/B7-1 interaction prevents epitope spreading and clinical relapses of murine EAE

Stephen D. Miller, Carol L. Vanderlugt, Deborah J. Lenschow, Jonathan G. Pope, Nitin J. Karandikar, Mauro C. Dal Canto, Jeffrey A. Bluestone

Research output: Contribution to journalArticle

297 Scopus citations

Abstract

Relapsing experimental autoimmune encephalomyelitis (R-EAE) induced with the immunodominant epitope from proteolipid protein, PLP139-151, is characterized by the development of recurrent relapses with recruitment of T cells reactive to additional myelin peptides, including PLP179-191 (epitope spreading). In this study, we have determined that the CD28/B7 costimulatory pathway is involved in this process. We found preferential up-regulation of B7-1 during the course of R-EAE and a selective increase in its functional costimulatory activity, relative to B7-2. Anti B7-1 F(ab) fragment therapy, but not anti B7-2 MAb therapy, blocked clinical relapses, ameliorated CNS pathology, and blocked epitope spreading. These results suggest that the maintenance of autoimmune reactivity in EAE depends on CD28/B7-1-dependent costimulation of newly recruited T cells responsible for epitope spreading. These studies have important implications for the role of epitope spreading in disease progression and the clinical application of costimulatory antagonists in autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)739-745
Number of pages7
JournalImmunity
Volume3
Issue number6
DOIs
StatePublished - Dec 1995

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Miller, S. D., Vanderlugt, C. L., Lenschow, D. J., Pope, J. G., Karandikar, N. J., Dal Canto, M. C., & Bluestone, J. A. (1995). Blockade of CD28/B7-1 interaction prevents epitope spreading and clinical relapses of murine EAE. Immunity, 3(6), 739-745. https://doi.org/10.1016/1074-7613(95)90063-2