Consequences of Fas-ligand and perforin expression by colon T cells in a mouse model of inflammatory bowel disease

S. J. Simpson, Y. P. De Jong, S. A. Shah, M. Comiskey, B. Wang, J. A. Spielman, E. R. Podack, E. Mizoguchi, A. K. Bhan, C. Terhorst

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21 Scopus citations

Abstract

Background and 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.

Original languageEnglish (US)
Pages (from-to)849-855
Number of pages7
JournalGastroenterology
Volume115
Issue number4
DOIs
StatePublished - Jan 1 1998

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Simpson, S. J., De Jong, Y. P., Shah, S. A., Comiskey, M., Wang, B., Spielman, J. A., Podack, E. R., Mizoguchi, E., Bhan, A. K., & Terhorst, C. (1998). Consequences of Fas-ligand and perforin expression by colon T cells in a mouse model of inflammatory bowel disease. Gastroenterology, 115(4), 849-855. https://doi.org/10.1016/S0016-5085(98)70256-2