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

本研究以近交系Lew(RT1A1)和ACI(RT1Aa)大鼠(6~8周龄)为供体，观察含CTLA4-Ig基因的重组腺病毒载体(AdexCTLA4-Ig)对同种异体肢体移植后排斥反应的影响。第1组：未处理组(n=5)。第2组：大鼠(n=4)静脉注射1×10~(-8)pfu(空斑形成单位)AdexCTLA4-IG。第3组：大鼠(n=4)注射1×10~(-9)pfu的Adex CTLA4Ig。组1的移植物在1周内发生急性排斥反应(MST：平均存活时间4.2±0.7天)，而组2和组3的移植物均能延长存活时间(MST 35.0±12.0天和14.5±4.0天)。但在我们的同种异体大鼠移植模型中，我们不能获得免疫耐受。对于进一步的实验，将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.