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

Gastroenterology. 1998 Oct;115(4):849-55. doi: 10.1016/s0016-5085(98)70256-2.


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 Tg26 mice (BM-->Tg26). 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 (PFPnull mice) or both molecules were used to reconstitute Tg26 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-->Tg26 animals.

Conclusions: Colon T cells from BM-->Tg26 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-->Tg26 colitis model.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Colon / metabolism*
  • Colon / pathology
  • Fas Ligand Protein
  • Inflammatory Bowel Diseases / metabolism*
  • Inflammatory Bowel Diseases / pathology
  • Inflammatory Bowel Diseases / physiopathology
  • Membrane Glycoproteins / metabolism*
  • Membrane Glycoproteins / physiology
  • Mice
  • Mice, Mutant Strains
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • T-Lymphocytes, Cytotoxic / metabolism
  • T-Lymphocytes, Cytotoxic / physiology*
  • Wasting Syndrome / physiopathology


  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Perforin