Zhang J, Li H, Jiang N, Zhang Q, Wang G-S, Yi H-M, Fu B-S, Wang G-Y, Yang Y, Chen G-H
Department of Liver Transplantation, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
Transplant Proc. 2010 Jun;42(5):1835-7. doi: 10.1016/j.transproceed.2010.01.065.
Blockade of a costimulatory pathway by adenovirus-mediated cytotoxic T lymphocyte associated antigen 4 immunoglobulin (CTLA4-Ig) gene transfer and anti-CD40L mAb(MR1) have been reported to enhance graft survival in several experimental transplantation models. In this study, we investigated the effects of gene transfer of CTLA4Ig and MR1 on islet xenograft rejection in mice. Recombinant adenovirus AdCTLA4Ig was constructed to express CTLA4Ig. Islet grafts from adult male DA rats transferred with AdCTLA4Ig were transplanted to streptozocin-induced diabetic Balb/c mice. The diabetic mice were treated with MR1 after transplantation. We evaluated the islet xenograft mean survival time as well as changes in interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) levels in transplanted mice. The mean survival of islet xenografts in the MR1 treatment group was 34.9 +/- 5.62 days, in the AdCTLA4Ig treatment group it was 56.5 +/- 10.64 days, and in the AdCTLA4Ig plus MR1 treatment group it was 112.9 +/- 19.26 days, all significantly prolonged compared with an untreated group (8.1 +/- 0.83 days). Within 1 week after transplantation the levels of IL-2 and TNF-alpha showed sharp increases in the untreated group, being significantly higher than those observed prior to transplantation. In conclusion, using both AdCTLA4Ig and MR1 can improve the islet xenograft survival. The beneficial effects of the combined use of the 2 reagents were superior to either 1 alone, possibly related to down-regulated expression of Th1 cell-related cytokines.
据报道，在多个实验性移植模型中，通过腺病毒介导的细胞毒性T淋巴细胞相关抗原4免疫球蛋白（CTLA4-Ig）基因转移和抗CD40L单克隆抗体（MR1）阻断共刺激途径可提高移植物存活率。在本研究中，我们调查了CTLA4Ig和MR1基因转移对小鼠胰岛异种移植排斥反应的影响。构建重组腺病毒AdCTLA4Ig以表达CTLA4Ig。将转染AdCTLA4Ig的成年雄性DA大鼠的胰岛移植到链脲佐菌素诱导的糖尿病Balb/c小鼠体内。移植后用MR1治疗糖尿病小鼠。我们评估了胰岛异种移植的平均存活时间以及移植小鼠中白细胞介素-2（IL-2）和肿瘤坏死因子-α（TNF-α）水平的变化。MR1治疗组胰岛异种移植的平均存活时间为34.9±5.62天，AdCTLA4Ig治疗组为56.5±10.64天，AdCTLA4Ig加MR1治疗组为112.9±19.26天，与未治疗组（8.1±0.83天）相比均显著延长。移植后1周内，未治疗组的IL-2和TNF-α水平急剧升高，显著高于移植前观察到的水平。总之，联合使用AdCTLA4Ig和MR1可提高胰岛异种移植的存活率。两种试剂联合使用的有益效果优于单独使用任何一种，可能与Th1细胞相关细胞因子的表达下调有关。
