title: Ectopic expression of Fas Ligand on cardiomyocytes renders cardiac allografts resistant to CD4(+) T-cell mediated rejection.
abstract: Fas Ligand limits inflammatory injury and permits allograft survival by inducing apoptosis of Fas-bearing lymphocytes. Previous studies have shown that the CD4(+) T-cell is both sufficient and required for murine cardiac allograft rejection. Here, utilizing a transgenic mouse that over-expresses Fas Ligand specifically on cardiomyocytes as heart donors, we sought to determine if Fas Ligand on graft parenchymal cells could resist CD4(+) T-cell mediated rejection. When transplanted into fully immunocompetent BALB/c recipients Fas Ligand transgenic hearts were acutely rejected. However, when transplanted into CD4(+) T-cell reconstituted BALB/c-rag(-/-) recipients, Fas Ligand hearts demonstrated long-term survival. These results indicate that Fas Ligand over-expression on cardiomyocytes can indeed resist CD4(+) T-cell mediated cardiac rejection and suggests contact dependence between Fas Ligand expressing graft parenchymal cells and the effector CD4(+) T-cells.
authors.affiliation: Department of Surgery, Colorado Center for Transplantation Care, Research and Education, University of Colorado Denver, 1775 Aurora Ct., Aurora, CO 80045, USA; Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver, 12631 E. 17th Ave, Aurora, CO 80045, USA. Electronic address: Robert.Plenter@ucdenver.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Plenter
authors.affiliation: Department of Surgery, Colorado Center for Transplantation Care, Research and Education, University of Colorado Denver, 1775 Aurora Ct., Aurora, CO 80045, USA; Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver, 12631 E. 17th Ave, Aurora, CO 80045, USA. Electronic address: Todd.Grazia@ucdenver.edu.
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Grazia
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital, 3333 Burnet Ave, Cincinnati, OH 45229, USA. Electronic address: David.Nelson@cchmc.org.
authors.forename: David P
authors.initials: DP
authors.lastname: Nelson
authors.affiliation: Department of Surgery, Colorado Center for Transplantation Care, Research and Education, University of Colorado Denver, 1775 Aurora Ct., Aurora, CO 80045, USA; Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver, 12631 E. 17th Ave, Aurora, CO 80045, USA. Electronic address: Marty.Zamora@ucdenver.edu.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Zamora
authors.affiliation: Department of Surgery, Colorado Center for Transplantation Care, Research and Education, University of Colorado Denver, 1775 Aurora Ct., Aurora, CO 80045, USA. Electronic address: Ronald.Gill@ucdenver.edu.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Gill
authors.affiliation: Department of Surgery, Colorado Center for Transplantation Care, Research and Education, University of Colorado Denver, 1775 Aurora Ct., Aurora, CO 80045, USA; Cardiology, Department of Pediatrics, The Colorado Children's Hospital, 13123 E. 16th Ave, Aurora, CO 80045, USA. Electronic address: Bill.Pietra@ucdenver.edu.
authors.forename: Biagio A
authors.initials: BA
authors.lastname: Pietra
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D053222:Fas Ligand Protein / Q000235:genetics / Q000276:immunology*; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression / Q000276:immunology*; D016654:Genes, RAG-1 / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival / Q000235:genetics* / Q000276:immunology; D016027:Heart Transplantation; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000166:cytology / Q000276:immunology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000276:immunology; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous
chemical_list: D053222:Fas Ligand Protein
keywords: Fas Ligand; Rejection; Transplantation