title: CTLA4-Fas ligand gene transfer mediated by adenovirus induce long-time survival of murine cardiac allografts.
abstract: BACKGROUND
  Fas ligand gene transfer to induce peripheral allograft tolerance in animal models has shown controversial results. The immunosuppression effects mediated by engineered FasL depend on whether alloreactive T cells are selectively deleted. In the present study, we tested the feasibility of a strategy to induce long-time survival by fusing CTLA4-FasL gene transfer in vivo.
  
  
  METHODS
  Cardiac allografts from DA(RT-1(a)) rats were transplanted heterotopically into the abdomens of LEW(RT-1(1)) rats. Plaque units (5x10(9)) of either AdCTLA4-FasL, AdCTLA4Ig, or AdEGFP were administered via the portal vein immediately after cardiac transplantation. The frequencies of helper T lymphocyte precursors (HTLp) and cytotoxic T lymphocyte precursors (CTLp) were determined by a combined single limiting dilution assay on days 5 and 20 after transplantation.
  
  
  RESULTS
  Cardiac allograft survival was significantly prolonged by either AdCTLA4-FasL or AdCTLA4Ig treatment(mean survival times [MST] of 71.0 +/- 3.7 and 45.7 +/- 2.4, respectively, n = 6) compared with untreated hosts or animals treated with AdEGFP(MST of 5.7 +/- 0.5 and 5.2 +/- 0.4, respectively, n = 6). In addition, treatment with AdCTLA4-FasL led to significantly prolonged allograft survival compared with AdCTLA4Ig treatment. Furthermore, the frequencies of HTLp and CTLp on day 20 among rats treated with AdCTLA4-FasL was lower than those on day 5, whereas frequencies of HTLp and CTLp on day 20 were similar with those on day 5 in the other groups.
  
  
  CONCLUSIONS
  These results suggest that administration of an adenovirus encoding fusion CTLA4-FasL gene to rat recipients effectively decreased the size of alloreactive T cells and induced long-term survival of cardiac allografts.
authors.affiliation: Department of Immunology, Immunological Institution, 38 Xueyuan Road, Beijing 100083, China. yg_feng03@yahoo.com.cn
authors.forename: Y-G
authors.initials: YG
authors.lastname: Feng
authors.forename: Y-Z
authors.initials: YZ
authors.lastname: Jin
authors.forename: Q-Y
authors.initials: QY
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Hao
authors.forename: G-M
authors.initials: GM
authors.lastname: Wang
authors.forename: S S
authors.initials: SS
authors.lastname: Xie
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D053222:Fas Ligand Protein; D018014:Gene Transfer Techniques; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics*; D023421:Models, Animal; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic; D014184:Transplantation, Homologous
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556708:Ctla4 protein, rat; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins