Antigen Presentation in the Gut

The induction of T cell responses requires recognition of antigensin association with class II major histocompatibility complex (MHC) proteinsand specialized antigen-presenting cells. Candidate antigen-presenting cells inthe gut include dendritic cells, macrophages, B lymphocytes, mucosal epithelialcells and endothelial cells. Dendritic cells isolated from normal human colon arepotent inducers of primary immune responses and express high levels of class lIMHC proteins. Lamina propria macrophages display class II MHC proteins, canpresent antigens to sensitized T cells, may process antigen and release interleukin-l, but suppress antigen presentation by intestinal dendritic cells in adose-dependent manner. Class II MHC molecules are normally expressed onsmall intestinal epithelial cells but not on normal colonic epithelial cells.Suppressor T cells and unresponsive T helper cells in the mucosa appear tomediate systemic T cell tolerance of dietary antigens. In the inflamed colon thereis infiltration of the lamina propria by large numbers of monocytes which secreteinterleukin-1, and the release of interferon-gamma appears to induce class IIprotein expression on colonic epithelial cells. Colonic epithelial cells frominflamed bowel may preferentially stimulate T helper cells so that local inductionof class II MHC molecules on epithelial cells may amplify and localize secondaryimmune responses at the site of inflamed mucosa. Taken together, the aberrantexpression of class II MHC molecules, breaches in epithelial cell integrity(resulting m exposure to luminal antigens including endotoxin and the increasednumbers of monocytes found 10 inflamed mucosa suggest that theresulting distortions in antigen presentation contribute to the localization andpersistence of the inflammatory lesion in inflammatory bowel disease