title: Accelerated rejection of Fas ligand-expressing heart grafts.
abstract: The Fas/Fas ligand (FasL) system plays an important role in the induction of lymphoid apoptosis and has been implicated in the suppression of immune responses. Recently, there has been renewed interest in immune privilege, as it was shown that two privileged sites (the eye and testes) constitutively express FasL, which kills lymphoid cells that invade these areas. We have established murine FasL-transgenic mice (B6) under the control of the cardiac alpha-myosin heavy chain promotor, and transplanted FasL-expressing F1(B6 x C3H/HeJ) heart grafts into syngeneic (F1) and allogeneic (C3H/HeJ) recipients. FasL-expressing F1 heart allografts placed in C3H/HeJ recipients as well as FasL-expressing F1 isografts placed in nontransgenic and FasL-transgenic F1 were more rapidly rejected, and their survival was much shorter than that of nontransgenic control F1 allografts placed in C3H/HeJ. Native control and FasL-expressing hearts looked normal in mice up to 8 wk of age on hematoxylin-eosin staining. Control heart allografts undergoing ordinally acute rejection showed moderate focal lymphocyte infiltrates, while FasL-expressing F1 allografts and isografts showed massive hemorrhage, edema, and massive neutrophil infiltration as early as 1 day after transplantation. In conclusion, FasL expression and surgical procedure (ischemia/reperfusion) were synergistic in the induction of accelerated heart graft rejection, while allogenicity was not necessary. It may be necessary to find ways of controlling neutrophilic reaction/apoptosis in infiltrating lymphocytes to use FasL in clinical organ transplantation.
authors.affiliation: Department of Urology, Faculty of Medicine, University of Tokyo, Japan. TAKEUCHI-URO@h.u-tokyo.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Takeuchi
authors.forename: T
authors.initials: T
authors.lastname: Ueki
authors.forename: H
authors.initials: H
authors.lastname: Nishimatsu
authors.forename: T
authors.initials: T
authors.lastname: Kajiwara
authors.forename: T
authors.initials: T
authors.lastname: Ishida
authors.forename: K
authors.initials: K
authors.lastname: Jishage
authors.forename: O
authors.initials: O
authors.lastname: Ueda
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: B
authors.initials: B
authors.lastname: Li
authors.forename: N
authors.initials: N
authors.lastname: Moriyama
authors.forename: T
authors.initials: T
authors.lastname: Kitamura
mesh_terms: D000818:Animals; D053222:Fas Ligand Protein; D005260:Female; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019076:Transgenes / Q000276:immunology; D019014:fas Receptor / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor