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[重组核小体通用Th细胞表位诱导系统性红斑狼疮样小鼠模型的口服免疫耐受]

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

作者信息

Zhou Chun-Li, Hao Jin, Tang Shu-Qian, Zhong Bai-Yu, Hao Fei

机构信息

Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2009 Jun 23;89(24):1702-6.

PMID:19957531
Abstract

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 antinucleosome 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-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 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.

摘要

目的

探讨通过减毒鼠伤寒沙门氏菌诱导核小体Th细胞表位所致系统性红斑狼疮(SLE)样模型口服免疫耐受的可行性。

方法

用凋亡的同基因淋巴细胞免疫建立SLE样小鼠模型。口服给予重组菌株以诱导免疫耐受。评估血清自身抗体水平,如抗核抗体(ANA)、双链DNA(ds-DNA)和抗核小体抗体、白细胞减少、蛋白尿和肾损伤情况。

结果

成功建立SLE样小鼠模型。与对照组相比,结果显示CTLA4-Ig-H2B组可显著降低血清自身抗体水平,如抗ANA、ds-DNA和抗核小体抗体,并改善白细胞减少和蛋白尿(均P<0.05)。CTLA4-Ig-H2B组肾小球中IgG免疫复合物沉积(1.35±0.16)低于CTLA4-Ig组(1.66±0.23)和H2B组(1.69±0.24)(均P<0.05)。CTLA4-Ig-H2B组肾小球病变评分(1.26±0.14)显著低于CTLA4-Ig组(1.73±0.25)和H2B组(1.71±0.20)(均P<0.05)。

结论

联合CTLA4-Ig,通过减毒鼠伤寒沙门氏菌诱导核小体Th细胞表位的SLE模型口服免疫耐受是可行的。这可能为通过口服免疫耐受预防和治疗SLE提供一种新方法。

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