Consequences of Fas-Ligand and Perforin Expression by Colon T Cells in a Mouse Model of Inflammatory Bowel Disease

Abstract Background & Aims: We describe a type of colitis that develops after transplantation of nonallogeneic wt bone marrow cells into T cell– and natural killer cell–deficient Tgϵ26 mice (BM→Tgϵ26). In these animals, severe wasting and inflammation of the colon correlates with the expansion of mucosal T lymphocytes that displays cytotoxic activity. The aims of this study were to determine the relative contribution of perforin and Fas ligand (Fas-L) expression to the cytotoxic action of these T cells and to examine the influence of each pathway in this model of colitis. Methods: Colonic T cells were tested for their ability to mediate Fas- and perforin-dependent killing in redirected cytotoxicity assays. Bone marrow cells from donor mice lacking either Fas-L ( gld mice) or perforin (PFP null mice) or both molecules were used to reconstitute Tgϵ26 mice. Results: Colon cytotoxic T lymphocyte displayed both Fas- and perforin-dependent killing. Deficiency in perforin, but not Fas-L, resulted in reduced incidence of wasting and, to a lesser extent, severe colitis in BM→Tgϵ26 animals. Conclusions: Colon T cells from BM→Tgϵ26 mice express both perforin and Fas-L. Although neither pathway is critical in the development of colitis, perforin does have a measurable influence on disease in the BM→Tgϵ26 colitis model. GASTROENTEROLOGY 1998;115:849-855