Fas-mediated cytotoxicity by intestinal intraepithelial lymphocytes during acute graft-versus-host disease in mice.
OBJECTIVE
Host-derived intestinal intraepithelial lymphocytes (IELs) increase in number during acute graft-versus-host disease (GVHD) in mice. In the present study, we examined Fas-mediated cytotoxicity by host-derived IELs against Fas-expressing target cells to see whether 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 F1 mice. The expression of Fas antigen on the intestinal epithelial cells (IECs) was examined by flow cytometry, and the expression of messenger RNA (mRNA) for Fas-L, interleukin 2, and interferon gamma in host-derived IELs was assessed by reverse-transcription polymerase chain reaction. Fas-mediated cytotoxicity by host-derived IELs was assessed using Fas-transfected cells, IECs, and Fas immunoglobulin Fc fusion protein (Fas Fc).


RESULTS
Fas antigen was constitutively expressed on the cell surface of IECs before and after GVHD induction. Although Fas-L mRNA was not detected or detected scarcely in either alphabeta or gammadelta IELs before GVHD induction, both IELs expressed high levels of mRNA for Fas-L and interferon gamma after GVHD induction. Host-derived IELs during acute GVHD showed cytotoxicity against Fas-transfected target cells and IECs, which was partly blocked by addition of Fas Fc.


CONCLUSIONS
Fas/Fas-L-mediated cytotoxicity by host-derived IELs may be partly responsible for the enteropathy during acute GVHD.
Sakai
T
T
First Department of Internal Medicine, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Showa-ku, Japan.
Kimura
Y
Y
Inagaki-Ohara
K
K
Kusugami
K
K
Lynch
D H
DH
Yoshikai
Y
Y
D000818:Animals; D015139:Blotting, Southern; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D004847:Epithelial Cells; D053222:Fas Ligand Protein; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D007410:Intestinal Diseases / Q000276:immunology; D007421:Intestine, Small / Q000166:cytology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D019014:fas Receptor / Q000276:immunology*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019014:fas Receptor