A synthetic mimetic of CD4 is able to suppress disease in a rodent model of immune colitis

CD4(+) mucosal T cells mediate the intestinal inflammation in Crohn's disea se and may serve as an important target for immune intervention. Here we as sessed the therapeutic effect of a synthetic mimetic of CD4 designed to mim ic both the sequence and conformation of the complementarity-determining re gion 3 of murine CD4 V1 domain (rD-mPGPtide) in a mouse colitis model using immunization with 2,4,6-trinitrobenzene sulfonic acid (TNB). i.v. administ ration of the rD-mPGPtide but not control scrambled peptide could suppress severe inflammation in the chronic colitis mouse model. After treatment wit h the rD-mPGPtide, a striking improvement of diarrhea and acute wasting dis ease was observed with decreased mortality. Serum anti-TNB antibody titers, CD45RB(low)CD4(+) T cells in the lamina propria and IFN-gamma mRNA express ion in the mucosa were significantly decreased with the rD-mPGPtide treatme nt. Anti-CD4 antibody also suppressed disease by depletion of CD45RB(high)C D4(+) T cells in the colonic mucosa. The observation that the synthetically engineered analogue of murine CD4 inhibits inflammation in a rodent diseas e model by different mechanisms than anti-CD4 antibody suggests that a huma n version of this peptide has potential therapeutic utility in CD4(+) mucos al T cell-mediated intestinal inflammation in Crohn's disease.