Contribution of Fas ligand to cardiac allograft rejection.
Effector mechanisms for allograft injury remain unclear. In the present study, we verified the contribution of Fas and Fas ligand (FasL) to cardiac allograft rejection by utilizing the Fas-deficient lpr or FasL-deficient gld mice as the donor or recipient. Cardiac myocytes prepared from normal mice, but not those from lpr mice, constitutively expressed Fas and were susceptible to FasL-mediated lysis. Survival of cardiac allografts was substantially prolonged when gld or lpr mice were used as the recipient. In contrast, cardiac allografts from lpr mice were normally rejected without a delay. Histological examination of the grafts in the gld or lpr recipients demonstrated a lesser cellular infiltration and much milder myocyte damage. Proliferative response and cytotoxic T lymphocyte induction against the donor-type alloantigens were not impaired in the gld or lpr recipients. These results indicate a substantial contribution of FasL to cardiac allograft rejection, independent of Fas in the grafts. This ralses a possibility that FasL may be more generally involved in tissue damage associated with various diseases than expected from the expression of Fas in the target organs.
Seino
K
K
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
Kayagaki
N
N
Bashuda
H
H
Okumura
K
K
Yagita
H
H
D000818:Animals; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D018076:DNA, Complementary / Q000235:genetics; D053222:Fas Ligand Protein; D005260:Female; D005318:Fetal Heart / Q000166:cytology; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D016027:Heart Transplantation / Q000276:immunology*; D007940:Leukemia L5178 / Q000473:pathology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D009206:Myocardium / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D014184:Transplantation, Homologous / Q000276:immunology*; D019014:fas Receptor / Q000235:genetics / Q000502:physiology*
D018076:DNA, Complementary; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor