Suppression of colon inflammation by CD80 blockade: Evaluation in two murine models of inflammatory bowel disease

Rajaraman Eri, Krithika N. Kodumudi, Don John Summerlin, Mythily Srinivasan

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Background: Human inflammatory bowel disease (IBD) is a chronic condition mediated by aberrant immune responses to the luminal antigens by activated CD4+ T cells. The CD80/CD86: CD28/CD152 costimulatory pathways transmit signals critical for T cell activation and suppression. Macrophages and epithelial cells are the chief antigen-presenting cells in the gut. Macrophages from the IBD colon express significantly elevated levels of CD80 and CD86 costimulatory molecules. The CD28-CD80 interaction primarily participates in breaking the tolerance and inducing the immune response in murine models of colitis. Blockade of CD80-costimulatory axis is an attractive strategy in the treatment of IBD. Methods: Incorporating the structural information of the CD80: CD152 complex together with the preferences of interface residues to form polyproline type II helix, we designed novel peptide agents that selectively blocked CD80 receptor interactions. Results: Administration of CD80 blocking agent at the time of adoptive transfer prevented the SCID mice from CD4+CD45Rbhigh T-cell mediated colitis. Significantly, CD80-CAP (competitive antagonist peptide) treatment suppressed established inflammation in TNBS-induced colitis, a model for Th1-mediated Crohn's disease. The colons of the mice receiving the CD80 blocking agent appeared unaffected macroscopically and exhibited negligible microscopic inflammation. The CD80-CAP treatment was associated with significantly reduced Th1 cytokines in the colon. Conclusions: The CD80 blocking peptide appeared to mediate protection against colitis by inducing Th2 skewing of the cytokine response.

Original languageEnglish (US)
Pages (from-to)458-470
Number of pages13
JournalInflammatory bowel diseases
Volume14
Issue number4
DOIs
StatePublished - Apr 1 2008

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Keywords

  • CD80 blockade
  • IBD
  • Murine model

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

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