免疫抑制剂作为DNA疫苗佐剂的研究  

The immunosuppressants as adjuvants of DNA vaccine

作　　者：米简洁[1] 朱庆鸿[1] 付红烨[1] 刘越[1] 赵佳[1] 康友敏[1] 

机构地区：[1]中国农业大学生物学院农业生物技术国家重点实验室,北京100193

出　　处：《中国免疫学杂志》2010年第1期79-81,84,共4页Chinese Journal of Immunology

基　　金：教育部博士点新教师基金(200800191026);农业生物技术国家重点实验室开放课题(2009SKLAB08-2);中国农业大学科研启动金支持(10099071)

摘　　要：目的:探讨免疫抑制剂作为DNA疫苗佐剂的免疫效果及预防自主免疫疾病的效果。方法:将三种免疫抑制剂环孢素(CsA)、他克莫斯(FK506)和霉酚酸酯(MMF)作为多发性硬化症(MS)的DNA疫苗佐剂,共同肌肉注射免疫小鼠。取小鼠脾脏抗体染色后,用流式细胞仪检测调节性T细胞(Treg)的比例及T细胞增殖反应,检测树突细胞(DCs)成熟状态及分泌白介素10(IL-10)的变化,并在诱导EAE动物模型后,检测临床打分的变化。结果:免疫FK506作为MS的DNA疫苗佐剂组显著提高了Treg细胞的比例,T细胞增殖反应显著受到了抑制,DCs细胞成熟受到抑制且IL-10的表达显著升高,能够显著降低小鼠实验性变态反应性脑脊髓炎(EAE)的临床打分。结论:FK506能够作为DNA疫苗的佐剂,诱导Treg细胞的产生,使机体产生免疫耐受,并能够在一定程度上预防自主免疫疾病的发生,为自身免疫性疾病的预防和治疗提供新的方法和思路。Objective：To check the effect of immunosuppressants as adjuvants for DNA vaccine to prevent autoimmune disease. Methods： Three immunosuppressants, Cyclosporin A （ CsA ）, Tacrolimus （FK506） and Mycophenolate Mofetil （MMF） were combined with DNA vaccine of Multiple Sclerosis （MS） and injected intramuscularly. The splenocytes of immunized mice were checked for regulatory T cells （Treg）, T cell proliferation and maturation of dendritic cells（Dcs） as well as release of interleukin 10 （IL-10）. The immunized mice were induced asEAE animal model to check the preventive effect of FK506 as adjuvant. Results： More Treg cells were induced in the mice immunized with FK506 and DNA vaccine and also T cell proliferation was suppressed. DCs maturation was blocked and high level of IL-10 in DCs was induced in mice treated with FK506 and DNA vaccine. The clinic scores of EAE were significantly decreased in mice treated with FK506 and DNA vaccine com- pared with other control groups. Conclusion： FK506 as adjuvant of DNA vaccine can stimulate Treg cells and immune tolerance, then prevent from the autoimmune disease.

关 键 词：免疫抑制剂 DNA疫苗 佐剂 自主免疫疾病 

分 类 号：R392-33[医药卫生—免疫学]