Background: CBir1 is a dominant antigen with a role in innate and adaptive immunity in mouse models of colitis and antibodies to CBir1 are associated with severe human Crohn's disease (CD). Our aim was to determine whether CBir1 stimulates innate and antigen-specific T-cell responses in CD. We demonstrate that CBir1 enhanced IL-6 and IL-1β production by peripheral blood (PB) monocytes. Methods: Real time polymerase chain reaction (PCR) was used for measurement of IL6 and IL1 expression. [3H] thymidine was used to measure T cell proliferation and Elispot assay was used to measure IFNγ production. Results: IL-6 was signi.cantly increased in monocytes from CD compared to controls and ulcerative colitis (UC). Anti-CBir1+ patients and IL-6 was inversely correlated. A significant increase in CBir1-speci.c peripheral T-cell proliferation was more evident in cells from CD than controls and UC. CBir1 induced increased numbers of IFN-gamma± cells in lamina propria mononuclear cells (LPMC) from CD compared to UC and controls. Conclusions: CBir1 induces enhanced peripheral innate and peripheral and mucosal antigen-specific T-cell responses in CD. Consistent with results from the mouse, CBir1 immune activation could play a role in CD. Copyright © 2008 Crohn's & Colitis Foundation of America, Inc.