CD80 blockade suppresses inflammatory response to syngenic flora in TNBS colitis. (B100)

Abstract

Abstract Inflammatory bowel disease (IBD) is an immune-mediated inflammatory disorder of the gastrointestinal organ system characterized by chronic inflammation of the bowel with periods of exacerbation and remission. Considerable evidence suggests that IBD is a result of abnormal activation of CD4+ T cells to intestinal microflora. Therapies targeting T cell costimulation such as anti-CD80 (B7-1), anti-CD86(B7-2) mAb and CTLA-4 mAb have provided some insights on the control of intestinal mucosal inflammation. Recently short polyproline helical peptide designed to selectively inhibit CD80: receptor interactions has been reported. We investigated the therapeutic potential of this peptide in animal models of colitis. When administered at the time of transfer, the CD80 blocking peptide (500μg i.v.) protected the SCID mice from CD4+ CD45Rbhi mediated transfer colitis efficacy of this peptide. Significantly when administered at the time of boosting (day 6, 500μg i.v.), the CD80 binding peptide suppressed clinical and microscopic inflammation in TNBS colitis. The lamina propria lymphocytes isolated from CD80 binding peptide treated mice secreted significantly less IL-12p40 and IFN-g when stimulated with syngenic normal colon flora. Increased number of CD4+ mesenteric lymph node cells were annexin positive in CD80 binding peptide treated mice suggesting that peripheral deletion activated T cells as the mechanism of mediating protection.