CD103免疫毒素在同种胰岛移植中的应用

Application of CD103-immunotoxin in the islet allograft transplantation

目的 制备能体内杀伤CD103表达细胞的免疫毒素,观察其对同种胰岛移植排斥反应的影响.方法 将CD103抗体与植物毒素saporin耦联产生M290-SAP,以2 mg/kg剂量注入小鼠腹腔,实验分为磷酸盐缓冲液（PBS）、IgG-SAP、M290和M290-SAP组,用流式细胞术检测CD103阳性细胞的肖减,之后将M290-SAP应用于化学性糖尿病小鼠胰岛移植模型,观察胰岛有功能存活情况.结果 PBS、IgG-SAP和M290组,肠上皮内CD103＋CD8＋淋巴细胞占CD3＋淋巴细胞的百分比分别为70.9%、68.4%和79.5%,而M290-SAP组几乎降至0;M290-SAP也杀灭了CD103＋的胸腺细胞.M290-SAP组胰岛移植物存活时间（＞100 d,n=9）,明显优于未处理组、IgG-SAP和M290组（均在20d内排斥）（P＜0.01）.结论 M290-SAP消除CD103表达细胞能促进同种胰岛移植物长期存活.

Objective To develop an immunotoxin （M290-SAP） that selectively depleted CD103expressing cells in vivo and study the effect of M290-SAP on the pancreatic islet allograft rejection. Methods The CD103 antibody was conjugated with plant toxin （saporin） to produce M290-SAP. M290-SAP was intraperitoneally injected into mice at a dose of 2 mg/kg. The mice were divided into PBS, IgG-SAP,M290 and M290-SAP groups. CD103-positive cells were counted by flow cytometry. The islet allograft survival was observed in each treated group. Results The percentage of intestinal intraepithelial CD103 ＋CD8＋ lymphocytes in total CD3 ＋ lymphocytes was 70. 9%, 68.4% and 79. 5% in PBS, IgG-SAP and M290 groups, respectively, and that in M290-SAP group down to almost 0%. M290-SAP also abrogated the CD103＋ thymocytes. Islet graft survival time was （ 〉 100 days,n=9） in M290-SAP group, significantly longer than PBS group, IgG-SAP and M290 groups （islet allografts were rejected within 20 days） （P〈 0. 01 ）. Conclusion Elimination of CD103-expressing cells with M290-SAP can prolong long-term islet allograft survival.