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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 被引量:2

Induction of oral immune tolerance in systemic lupus erythematosus-like murine model by recombinant nucleosomal universal Th cell epitope
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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.
出处 《中华医学杂志》 CAS CSCD 北大核心 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)
关键词 核小体 表位 T淋巴细胞 沙门菌 鼠伤寒 免疫耐受 Nucleosomes Epitopes, T-lymphocyte Salmonella typhimurium Immune tolerance
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