免疫毒素IP10-DT390核酸制剂对实验性变态反应性脑脊髓炎的治疗作用

An Expression Plasmid Encoding Recombinant Immunotoxin IP10-DT390 Suppresses the Experimental Autoimmune Encephalomyelitis

研究重组免疫毒素杀伤活化T细胞后,对实验性变态反应性脑脊髓炎(EAE)的发生和发展产生的抑制作用。利用含有编码重组免疫毒素IP10-DT390的真核质粒,直接导入动物肌肉,使IP10-DT390在骨骼肌内表达,通过IP10-DT390对活化T细胞的选择性杀伤,探索对EAE的治疗效果。实验结果显示,这种新型免疫毒素核酸制剂可以减轻EAE模型鼠的发病症状、选择性的减少中枢系统自身活化的T淋巴细胞浸润、降低外周血T细胞数量,而对免疫反应的其他成分影响不明显。该免疫毒素核酸制剂可能成为治疗有关自身免疫性疾病的一种新的有效方法。

Experimental autoimmune encephalomyelitis （EAE） is an autoimmune disease of the central nervous system（CNS） ; it serves as a model for the human multiple sclerosis（MS）. In mice, EAE is mediated by T cells specific for various myelin basic proteins which migrate from the periphery to the CNS. In search of a way to prevent the induction and progression of EAE,we observed the effects of recombinant immunotoxin IP10-DT390 on blocking or eliminating the active T cells in the EAE model. In this paper is presented an experimental gene therapy-based model in which the mice were made resistant to EAE induction by plasmid DNA encoding recombinant immunotoxin that was injected into the leg muscles of mice. The new immuno-biological construct could selectively impair autoreactive T-cell homing while the duration of clinical signs is shorter, and the new construct would not affect other components of the immune response. These data demonstrated the effectiveness of the constructs in the treatment of EAE and suggested its usefulness in the treatment of other autoimmune diseases.