Heart Transplant Research Today is a free monthly online journal that collates and summarizes the latest research about Heart Transplant, including details on risks, prognosis, procedure, surgery, organ donation.

CTLA4-Fas ligand gene transfer mediated by adenovirus induce long-time survival of murine cardiac allografts.

Feng YG, Jin YZ, Zhang QY, Hao J, Wang GM, Xie SS

Department of Immunology, Immunological Institution, 38 Xueyuan Road, Beijing 100083, China. yg_feng03@yahoo.com.cn

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. CONCLUSION: 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.

Published 20 June 2005 in Transplant Proc, 37(5): 2379-81.
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