B7-H1基因修饰的调节性DC对小鼠甲状腺相关性眼病的治疗作用

Inhibition effect of B7-H1 gene-modified regulatory dendritic cells on thyroid-associated ophthalmopathy in mice

目的:构建表达小鼠B7-H1基因的腺病毒载体,转染修饰树突状细胞,并研究该细胞对小鼠甲状腺相关性眼病(thyroid-associated ophthalmopathy,TAO)的治疗效应。方法:设计并构建小鼠B7-H1的腺病毒表达载体,转染小鼠骨髓来源的树突状细胞,检测该树突状细胞的表型和功能,鉴定其对免疫应答的负向调控能力,采用实验动物模型观察B7-H1基因修饰的树突状细胞在体内治疗TAO的效果。结果:成功构建出具有良好B7-H1表达效力的腺病毒载体,病毒滴度为1.8×109PFU/mL,转染腺病毒的小鼠骨髓来源的树突状细胞表现出调节性树突状细胞性能,能够负向抑制免疫应答;在动物模型中使用该型树突状细胞可以有效控制甲状腺眼病的发生发展。结论:成功构建了表达小鼠B7-H1基因的腺病毒表达载体,转染了该载体的树突状细胞具有调节性树突状细胞的性能,抑制正向免疫应答,能够有效抑制甲状腺眼病的发生发展,揭示基因修饰的树突状细胞可能成为治疗甲状腺眼病的潜在生物制剂。

AIM：To construct adenovirus vector expressing mice B7-H1 gene, transfect dendritic cells （ DCs ） , and to study the therapeutic effect of modified DC on thyroid-associated ophthalmopathy （ TAO） in mice. METHODS： We designed and constructed B7-H1 gene adenovirus expression vector, and transfected DCs from mouse bone marrow, tested the phenotype and function of modified DCs, identificated its negative regulation to immune responses. The modified DCs were infected the sicked mice. And then the immunotherapeutic effect of modified DCs to TAO were tested. RESULTS： B7 - H1 gene adenovirus vector was constructed and transfected DCs from bone marrow. The titer of the recombinant adenovirus was 1. 8í109 PFU/mL. B7-H1 gene modified DCs characteristics of regulatory DCs, could inhibit positive immune responses. The inhibition proceeding of TAO into mice infected modified DCs, was obviously prior to the control mice. The gene modified DCs, maybe become the new immunotherapy biological agent to thy TAO. CONCLUSION： We constructed the expression of mouse B7 - H1 gene adenovirus expressed vector successfully, transfected DCs, by vector have properties of regulatory DCs, inhibiting positive immune response and the occurrence and development of thyroid eye disease. Gene modified DCs, reveal potent to the treatment of thyroid eye disease.