重组核小体通用性Th表位诱导系统性红斑狼疮样小鼠模型口服免疫耐受  

Induction of oral immune tolerance in systemic lupus erythematosus-like murine model by recombinant nucleosomal universal 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

出　　处：《中华医学杂志》2009年第24期1702-1706,共5页National Medical Journal of China

基　　金：国家自然科学基金（30200258）

摘　　要：目的探讨直接应用活菌苗在肠道内表达核小体通用性Th表位抗原诱导系统性红斑狼疮（SLE）样小鼠模型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样小鼠模型，喂饲构建的重组减毒鼠伤寒沙门菌菌株进行口服免疫耐受的诱导。观察SLE样小鼠模型血清抗核抗体（ANA）、抗双链DNA抗体（抗ds—DNA抗体）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样小鼠模型。与对照组相比，CTLA4-Ig—H2B组小鼠ANA、ds．DNA和抗核小体抗体等自身抗体的水平均较低，白细胞减少和蛋白尿明显改善，差异均有统计学意义（均P〈0．05）。CTLA4-Ig—H2B组小鼠肾小球内免疫复合物沉积强度明显轻于CTLA4-Ig组和H2B组，差异均有统计学意义[积分（1．35±0．16）分比（1．66±0．23）分和（1．69±0．24）分，均P〈0．05]。CTLA4-Ig—H2B组肾小球病婵损害积分与CTLA4-Ig组和H2B组比较，差异均有统计学意义[（1．26±0．14）分比（1．73±0．25）分和（1．71±0．20）分，均P〈0．05]。结论利用减毒鼠伤寒沙门菌携带核小体Th细胞表位肽H2B14-28诱导SLE的口服免疫耐受足可行的，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 systemic lupus erythematosus（ SLE）-like model induced by nucleosomal Th cell epitope via the attenuated Salmonella typhimurium. Methods SLE-like murine model was established by immunization with apoptotie 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, leukopenia, proteinuria and kidney injuries were evaluated. Results SLE-like routine model was successfully established. Compared with controls, it was shown that CTLA4-Ig-H2B group could dramatically reduce the levels of serum autoantibodies, such as anti-ANA, ds-DNA and antinucleosome antibody and ameliorate leukopenia and proteinuria （ all P 〈 0. 05）. hnmune complex deposits of IgG in glomeruli were Dower in CTLA4-Ig-H2B （1.35±0.16）than in CTLA4-Ig （1. 66 ± 0. 23 ） and H2B （1. 69 ± 0. 24 ） （ both P〈0.05）. The score of glomeruli lesion of CTLA4-Ig-H2B （ 1.26 ±0. 14） was significantly lower than those of CTLA4-Ig（ 1.73 ±0.25）and H2B（1.71 ±0.20） （both P〈0.05）. Conclusion Combined with CTLA4-Ig, it is feasible to induce oral immune tolerance of SI,E models with nucleosomal Th cell epitope via the attenuated Salmonella typhimurium. This may provide a novel way to prevent and treat SLE by oral immune tolerance.

关 键 词：核小体 表位 T淋巴细胞 沙门菌 鼠伤寒 免疫耐受 

分 类 号：R686[医药卫生—骨科学]