Because the mucosal immune system is continuously exposed to a myriad of potentially harmful environmental antigens, it frequently reacts with antiinflammatory/regulatory T cell responses driven by TGF-β-producing T H 3 cells and IL-10-producing regulatory T cells. Intestinal inflammation in patients with inflammatory bowel diseases is thought to result from an overwhelming uncontrolled activation of the mucosal immune system induced by antigens of the normal luminal flora in genetically susceptible individuals. Inflammatory bowel disease appears to be mediated by subsets of CD4+ T lymphocytes or NK T cells secreting high levels of proinflammatory cytokines such as TNF-α. The increased expression of integrins/addressins in the inflamed gut and the increased expression of adhesion molecules on T cells facilitate migration of these pathogenic T cell subsets into the lamina propria. Additionally, the local activation of antiapoptotic pathways in pathogenic T lymphocytes leads to a further accumulation of these cells in the lamina propria, causing perpetuation and chronicity of inflammatory bowel disease. This concept is underlined by the finding that most potent immunosuppressive drugs used in treatment of inflammatory bowel disease seem to work by inducing T cell apoptosis via inhibition of STAT-3 and NFκB-dependent antiapoptotic pathways. Taken together, distinct T cell subsets appear to act as mediators or guardians of inflammatory bowel disease, and thus they play a central role in controlling the delicate balance between proinflammatory and antiinflammatory immune responses in the gut.