Treatment with intact anti-B7-1 mAb during disease remission enhances epitope spreading and exacerbates relapses in R-EAE

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

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Abstract

PLP139-151-induced experimental autoimmune encephalomyelitis in the SJL mouse is a Th1-mediated inflammatory demyelinating disease characterized by a relapsing-remitting clinical course (R-EAE). Clinical relapses are mediated by T cells specific for a non-cross reactive secondary PLP epitope (PLP178- 191) induced by epitope spreading. We have previously shown that B7-1 expression is upregulated in SJL mice undergoing R-EAE and in vivo treatment during remission with F(ab) fragments of anti-B7-1 mAb, blocked epitope spreading and disease progression. In contrast, the present study shows that treatment with intact anti-B7-1 mAb exacerbated clinical disease relapses and enhanced CNS demyelination. Anti-B7-1-treated mice showed enhanced in vivo delayed-type hypersensitivity (DTH) to the relapse-associated PLP178-191 epitope and responses to the immunodominant MBP84-104 epitope which are absent in the controls. Thus, ligation of B7-1 by intact mAbs has effects opposite to those of anti-B7-1 F(ab) fragments suggesting that the mAb is directly signaling through B7-1 expressed on T cells and/or APCs.

Original languageEnglish (US)
Pages (from-to)113-118
Number of pages6
JournalJournal of Neuroimmunology
Volume79
Issue number2
DOIs
StatePublished - Nov 1997

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Keywords

  • B7-1
  • Epitope spreading
  • Experimental autoimmune encephalomyelitis
  • Proteolipid protein
  • SJL/J mice
  • T cell costimulation

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

Vanderlugt, C. L., Karandikar, N. J., Lenschow, D. J., Dal Canto, M. C., Bluestone, J. A., & Miller, S. D. (1997). Treatment with intact anti-B7-1 mAb during disease remission enhances epitope spreading and exacerbates relapses in R-EAE. Journal of Neuroimmunology, 79(2), 113-118. https://doi.org/10.1016/S0165-5728(97)00108-2