A critical role for B7/CD28 costimulation in experimental autoimmune encephalomyelitis: A comparative study using costimulatory molecule-deficient mice and monoclonal antibody blockade

Ann M. Girvin, Mauro C. Dal Canto, Lesley Rhee, Benoît Salomon, Arlene Sharpe, Jeffrey A. Bluestone, Stephen D. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

The B7/CD28 pathway provides critical costimulatory signals required for complete T cell activation and has served as a potential target for immunotherapeutic strategies designed to regulate autoimmune diseases. This study was designed to examine the roles of CD28 and its individual ligands, B7-1 and B7-2, in experimental autoimmune encephalomyelitis (EAE), a Th1- mediated inflammatory disease of the CNS. EAE induction in CD28- or B7- deficient nonobese diabetic (NOD) mice was compared with the effects of B7/CD28 blockade using Abs in wild-type NOD mice. Disease severity was significantly reduced in CD28-deficient as well as anti-B7-1/B7-2-treated NOD mice. B7-2 appeared to play the more dominant role as there was a moderate decrease in disease incidence and severity in B7-2-deficient animals. EAE resistance was not due to the lack of effective priming of the myelin peptide-specific T cells in vivo. T cells isolated from CD28-deficient animals produced equivalent amounts of IFN-γ and TNF-α in response to the immunogen, proteolipid protein 56-70. In fact, IFN-γ and TNF-α production by Ag-specific T cells was enhanced in both the B7-1 and B7-2-deficient NOD mice. In contrast, peptide-specific delayed-type hypersensitivity responses in these animals were significantly decreased, suggesting a critical role for CD28 costimulation in in vivo trafficking and systemic immunity. Collectively, these results support a critical role for CD28 costimulation in EAE induction.

Original languageEnglish (US)
Pages (from-to)136-143
Number of pages8
JournalJournal of Immunology
Volume164
Issue number1
DOIs
StatePublished - Jan 1 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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