Prolonged survival of limb allografts in rats treated with CTLA4-Ig gene transfer using adenoviral vector

在这项研究中，我们研究了含有CTLA4-Ig的重组腺病毒载体（AdexCTLA4-Ig）对大鼠血管化肢体移植后的排斥反应的影响。近交系大鼠LEW （RTlAl）和ACI (RTlAa)（6 ~ 8周龄）分别作为移植受体和供体。供体ACI大鼠的血管化腿与受体LEW大鼠的股动脉、股静脉吻合。各组在移植当日按以下方式进行术后治疗。第1组：大鼠（n=5）未经治疗。第二组：大鼠（n=4）经尾静脉给予1*10^8 PFU（斑块形成单位）体积的AdexCTLA4-IG。第三组：大鼠（n=4）给予1*10^9 PFU的Adex CTLA4Ig。组1在1周内出现急性排斥反应（MST：平均生存时间4.2*0.7天），而组2和组3均表现出延长生存时间（MST: 35.0*12.0和14.5*4.0天）。在我们的研究中，AdexCTLA4-Ig的转导可显著延长LEW大鼠ACI肢体移植物的存活时间。但在同种异体移植大鼠模型中不能获得免疫耐受。在进一步的实验中，还需要添加其他技术来持续延长同种异体肢体移植的存活时间。

In this study, we exanined the effect of recoambinant adenovirus vector containing CTLA4-Ig (AdexCTLA4-Ig) to modify the rejection process observed after vascularized limb allo-transplantation in rats.Inbred LEW (RTlAl) and ACI (RTlAa) rats (6 to 8 weeks old) were used as transplant recipients and donors respectively.The vascularized leg of the donor ACI rat was anastomosed to the femoral artery and vein of the recipient LEW rat.Postoperative treatments were performed for each group in the fellowing manner at transplanted day. Group 1 : rats(n=5) were untreated. Group 2 : rats(n=4) were administered with a volume of 1*10^8 PFU (plaque forming units) of AdexCTLA4-IG via the teil vein. Group 3 : rats(n=4) were administered with 1*10^9 PFU of Adex CTLA4Ig. Allografts in group 1 were acutely rejected within one week(MST : mean survival time 4.2*0.7 days), Whereas both group2 and 3 allografts exhibited to prolong the survival(MST 35.0*12.0 and 14.5*4.0 days).In our studies, transduction of AdexCTLA4-Ig prolonged the survival of ACI limb grafts in LEW rats significantly. But we could not acquire immune tolerance in our rat allograft model. For further experients the addition of other technique will be needed to consistently prolong the survival of limb allograft.