Long-term Graft Acceptance in Rat Heart Transplantation by CTLA4Ig Gene Transfection Combined with FTY720 Treatment
| Autor: | Haruko Nagai, Shin Enosawa, Shohei Ogoshi, Masanao Ohba, Yusuke Kita, Seiichi Suzuki, Hiroshi Amemiya, Xiao-Kang Li, Naoko Funeshima, Hui-qi Zhang, Torayuki Okuyama, Shiro Sasaguri |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Immunoconjugates Recombinant Fusion Proteins Transfection Abatacept Andrology Immune system Antigens CD Sphingosine Immunopathology Gene expression Animals Medicine CTLA-4 Antigen Fingolimod Hydrochloride business.industry Graft Survival CD28 Antigens Differentiation Rats Intracellular signal transduction Transplantation surgical procedures operative Propylene Glycols Apoptosis Immunology Heart Transplantation Surgery business Immunosuppressive Agents |
| Zdroj: | World Journal of Surgery. 25:391-398 |
| ISSN: | 1432-2323 0364-2313 |
| DOI: | 10.1007/s002680020071 |
| Popis: | CTLA4Ig strongly adheres to B7 molecules on antigen-presenting cells to block intracellular signal transduction via CD28 on helper T cells, which eventually inhibits immune responses. We have demonstrated that the administration to recipient animals of adenoviral vectors containing CTLA4Ig gene (adCTLA4Ig) prolonged graft survival, although the gene expression diminished in a time-dependent manner and the grafts were finally rejected. In addition, recipient animals treated with FTY720, a new immunosuppressant, exhibited a decrease in the number of peripheral lymphocytes due to apoptosis. In this study, we performed adCTLA4Ig transfection combined with FTY720 treatment in heart-grafted rats to determine if the combination could induce a mutual effect on graft survival. The recipient animals were given injections of 1 x 10(9) plaque-forming units of adCTLA4Ig via the tail vein immediately after grafting. On the day before transplantation we administered FTY720 orally to some of these animals at a dosage of 5 mg/kg and again on the day of transplantation. The median graft survival period in the adCTLA4Ig-only group was 27 days, whereas that in the combination group was markedly prolonged to 56 days. Of 15 grafts, 5 survived indefinitely. In these groups we observed detectable levels of CTLA4Ig in the sera 49 days after grafting; the levels were always higher in the combination group than in the adCTLA4Ig-only group. As a result, this study revealed that FTY720 and adCTLA4Ig have a potent mutual effect on graft survival during rat heart transplantation. Furthermore, it is highly possible that FTY720 enhances gene expression of adCTLA4Ig, which may be related to the long-term acceptance of grafts. |
| Databáze: | OpenAIRE |
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