Institutional members access full text with Ovid®

Share this article on:

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

Eri, Rajaraman PhD1,*; Kodumudi, Krithika N. PhD1; Summerlin, Don John MS1; Srinivasan, Mythily MDS, PhD1,*

doi: 10.1002/ibd.20344
Original Basic Science Articles

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.

1 Department of Oral Pathology, Medicine and Radiology, School of Dentistry, Indiana University Purdue University at Indianapolis, Indianapolis, Indiana

* IBD Research Team, Mater Medical Research Institute, Raymond Terrace, Aubugny Place, South Brisbane Q 4101, Australia

* Department of Oral Pathology, Medicine and Radiology, 1121 W. Michigan St., Indianapolis, IN 46202 (e-mail: mysriniv@iupui.edu)

Received 27 July 2007; Accepted 22 October 2007

Published online 9 January 2008 in Wiley InterScience (www.interscience.wiley.com).

Grant sponsor: National Institutes of Health; Grant Number: RO3 AR051411-01; Grant sponsor: ‘First Award’ by Crohn's and Colitis Foundation of America.

© Crohn's & Colitis Foundation of America, Inc.
You currently do not have access to this article

To access this article:

Note: If your society membership provides full-access, you may need to login on your society website