Modulation of experimental autoimmune encephalomyelitis: Effect of altered peptide ligand on chemokine and chemokine receptor expression

Falko R. Fischer, Laura Santambrogio, Yi Luo, Michael A. Berman, Wayne W. Hancock, Martin E. Dorf

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Experimental autoimmune encephalomyelitis (EAE) is a T helper 1 (Th1) cell mediated demyelinating disease and the principal animal model for multiple sclerosis. Spinal cords from SJL mice primed with proteolipid protein peptide 139-151 (pPLP) expressed the chemokines RANTES, MCP-1, MIP-2, KC, MIP-1α, MIP-1β, Mig, and fractalkine. We also identified IP-10 in these samples and described a sequence polymorphism in this transcript. Chemokine expression was specific for tissues of the central nervous system. MCP-1, IP- 10, and MIP-2 RNA expression significantly correlated with clinical score. Chemokine receptor expression generally correlated with ligand expression. pPLP-primed mice expressed the Th1-associated markers CCR5 and CXCR3 on mononuclear cells. In addition, cells expressing CCR1, CCR2, CCR3, CCR4, CCR8, and CXCR2 were detected. Here we demonstrate that altered peptide ligand (APL)-induced protection from EAE was accompanied by modulation of chemokine and chemokine receptor expression. Spinal cord tissue sections from APL-protected mice showed greatly reduced levels of all chemokines and of CCR1, CCR5, CCR8, CXCR2 and CXCR3. The Th2-associated chemokine receptors CCR3 and CCR4 were found in protected mice, supporting the hypothesis that Th1 but not Th2 cells are down-regulated by APL treatment. This report concludes that chemokines and chemokine receptors can be useful tools to follow modulation of autoimmune disease. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)195-208
Number of pages14
JournalJournal of Neuroimmunology
Volume110
Issue number1-2
DOIs
StatePublished - Oct 2 2000

Keywords

  • Altered peptide ligand
  • Chemokine
  • Chemokine receptor
  • Experimental autoimmune encephalomyelitis
  • Th1/Th2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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