Mucosal T cell proliferation and apoptosis in inflammatory bowel disease

Abstract

Both forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), represent prototypical conditions whose most salient features are the presence of chronic inflammation involving various parts of the intestinal tract and an increased risk of cancer, which is a complication directly related to the duration and activity of gut inflammation. Several factors have been implicated in the unrelenting mucosal inflammation of IBD, prominent among them being the presence of a persistently elevated number of activated T cells in the mucosa of CD and UC patients. These T cells display various defects of proliferation and apoptosis, and these abnormalities are credited with directly contributing to the pathogenesis of IBD and possibly the progression to colon cancer. This notion is supported by the observation that T cells are also prominently found infiltrating most tumors and are functionally impaired compared to T cells in the circulation. This establishes a parallel that may constitute a link between chronic intestinal inflammation and the development of malignancies in the inflamed intestine. This article will review some of the basic features of human intestinal mucosal T cells, examine the mechanisms underlying the processes of cell cycling and cell death, describe the defective proliferative and apoptotic function detected in CD and UC, and discuss the implications of modulating T cell apoptosis in IBD for therapeutic purposes and eventually decreasing the risk of cancer development.