T-cell–induced mucosal damage in the intestine

Abstract

T cells are central to most inflammatory disorders of the intestine, particularly Celiac disease, graft vs. host disease, Crohn disease, and ulcerative colitis. The mechanisms by which T cells contribute to mucosal damage in these disorders have been explored using both in vitro and in vivo models. This review will highlight recent studies directed at understanding the mechanisms by which T cells are involved in the induction of mucosal damage. The recent studies of in vivo T-cell activation using monoclonal anti-CD3 antibody have shown that a number of cytotoxic T-cell pathways are required and involved in the induction of mucosal damage and in particular in the induction of epithelial cell apoptosis. These include the Fas/FasL and perforin pathways. Other mediators of T-cell-induced cytotoxicity, such as TNFalpha and IFNgamma may contribute to mucosal damage but are not required for the induction of mucosal damage in vivo. In addition, several studies have tried to identify the role of regulatory mucosal T cells and the physiologically relevant triggers for T-cell-induced mucosal damage. It is now clear that there are significant redundancies in the mechanisms that lead to immune-mediated mucosal damage and that the mechanisms that operate in vivo may not be predicted by in vitro experiments. These investigations are improving our understanding of the pathogenesis of immune-mediated enteropathies and will hopefully lead to new approaches to the management of these disorders.