Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Inflamm Bowel Dis. 2008 Apr;14(4):458-70. doi: 10.1002/ibd.20344.

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

Author information

  • 1Department of Oral Pathology, Medicine and Radiology, School of Dentistry, Indiana University Purdue University at Indianapolis, Indianapolis, Indiana 46202, USA.

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+CD45Rb(high) 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.

PMID:
18186109
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Lippincott Williams & Wilkins
    Loading ...
    Write to the Help Desk