重组pCDR1 Th表位诱导SLE口服免疫耐受的实验研究  

Experimental study of SLE oral immune tolerance induced by recombinant pCDR1 Th cell epitope

作　　者：周春丽[1] 郝进[2] 唐书谦[1] 钟白玉[1] 郝飞[1] 

机构地区：[1]第三军医大学西南医院皮肤科,重庆400038 [2]重庆医科大学附属第二医院皮肤科,400010

出　　处：《重庆医学》2009年第3期278-280,284,共4页Chongqing medicine

基　　金：国家自然科学基金资助项目(30200258)

摘　　要：目的探讨直接应用活菌苗在肠道内表达pCDR1Th表位抗原诱导SLE口服免疫耐受的可行性。方法以同系凋亡淋巴细胞免疫BALB/c小鼠制备SLE样症状小鼠模型,喂饲构建的重组SL7207菌株进行免疫耐受的诱导。观察血清ANA、ds-DNA和抗核小体抗体等自身抗体、白细胞、蛋白尿和肾脏损伤情况。结果成功制备了SLE鼠模型。与阴性对照组相比,CTLA4-Ig-pCDR1能明显降低实验小鼠ANA、ds-DNA和抗核小体抗体等自身抗体的水平,对白细胞减少和蛋白尿有明显的改善作用,对肾脏损伤有明显的保护作用。结论利用减毒鼠伤寒沙门菌携带pCDR1Th表位诱导SLE的口服免疫耐受是可行的,这为口服诱导免疫耐受防治SLE提供了一个新的途径。Objective To explore the feasibility of oral immune tolerance of SLE models induced by pCDR1 Th cell epitope via the attenuated Salmonella typhimurium. Methods SI.E like syndrome murine model was established by immunization with apoptotic syngeneic lymphocytes. The recombinant strains were orally administrated to induce immune tolerance. The levels of serum autoantibodies, such as anti ANA, ds DNA, and antinucleosome antibody, and leukopenia, proteinuria, and kidney injuries were evaluated. Results SLE-like syndrome murinc model was successfully established. Compared with negative controls,the findings showed that CTLA4-Ig-pCDR1 group could significantly reduce the levels of serum autoantibodies,such as anti-ANA,ds DNA,and antinucleosome antibody,and ameliorate the clinical manifestations of established experimental SLE such as leukopenia, proteinuria, and kidney injuries. Conclusion Combined with CTLA4-Ig,it is feasible to induce oral immune tolerance of SLE models with pCDR1 Th cell epitope via the attenuated Salmonella Typhimurium. This may provide a new way to prevent and treat SLE by oral immune tolerance.

关 键 词：系统性红斑狼疮 pCDR1 TH表位 CTLA4-IG 减毒鼠伤寒沙门菌 口服免疫耐受 

分 类 号：R593.241[医药卫生—内科学]