FAS-MEDIATED CYTOTOXICITY BY INTESTINAL INTRAEPITHELIAL LYMPHOCYTES DURING ACUTE GRAFT-VERSUS-HOST DISEASE IN MICE

Background & Aims: Host-derived intestinal intraepithelial lymphocytes (IELs) increase in number during acute graft-versus-host disease (GVH D) in mice, in the present study, we examined Fas-mediated cytotoxicit y by host-derived IELs against Fas-expressing target cells to see whet her Fas/Fas ligand (Fas-L) interaction is involved in the pathogenesis of enteropathy during acute GVHD. Methods: Acute GVHD was induced by injection of parental spleen cells into nonirradiated Fl mice. The exp ression of Fas antigen on tile intestinal epithelial cells (IECs) was examined by flow cytometry, and the expression of messenger RNA (mRNA) for Fas L, interleukin 2, and interfeuon gamma in host-derived IELs w as assessed by reverse-transcription polymerase chain reaction. Fas-me diated cytotoxicity by host-derived IELs was assessed using Fas-transf ected cells, IECs, and Fas immunoglobulin Fe fusion protein (Fas Fc). Results: Fas antigen was constitutively expressed on tile cell surface of IECs before and after GVHD induction. Although Fas-L mRNA was not detected or detected scarcely in either alpha beta or gamma delta IELs before GVHD induction, both IELs expressed high levels of mRNA for Fa s-L and interferon gamma after GVHD induction, Host-derived IELs durin g acute GVHD showed cytotoxicity against Fas-transfected target cells and IECs, which was partly blocked by addition of Fas Fc. Conclusions: Fas/FasL-mediated cytotoxicity by host-derived IELs may be partly res ponsible for the enteropathy during acute GVHD.