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

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,白细胞减少和蛋白球明显改善,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组肾小球病理损害积分与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.

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

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 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, leukopenia, proteinuria and kidney injuries were evaluated. Results SLE-like murine 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 antinucleoseme antibody and ameliorate leukopenia and proteinuria (all P<0.05). Immune complex deposits of IgG in glomeruli were lower 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 CTLA4-1g-tt2B(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 SLE 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.