The inflammatory bowel diseases (IBD), ulcerative colitis and Crohn's disease, are histologically characterized by an accumulation of lymphocytes and plasma cells in the lamina propria and foci of polymorphonuclear lymphocytes. An immune mechanism has long been suspected in the pathogenesis of IBD but, the etiology remains unknown. It is also not clear whether alterations in lymphocyte populations or their function mediate the mucosal injury or are epiphenomena of inflammation. Current research efforts investigating the functional properties of intestinal mucosal lymphocyte subpopulations, especially the intraepithelial lymphocytes (IEL), have been hampered by the inability to specifically identify IEL in cell suspension after isolation from intestinal specimens. The major goal of this project is to define possible phenotypic and functional differences in the mucosal lymphocyte subpopulations in IBD and normal intestine. This will be accomplished by using recently developed monoclonal antibodies that are primarily restricted to mucosal lymphocytes and IEL in particular. Monoclonal antibodies that recognize the T cell receptor gamma/delta will also be used to determine the intestinal distribution of these cells in IBD and their functional characteristics. A difference in the distribution or function of lymphocyte subpopulations in the lamina propria or epithelial compartments, may play a role in the pathogenesis of IBD.