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小鼠实验性自身免疫性肝炎的细胞免疫研究

Study of cellular immunity in experimental autoimmune hepatitis in mice.

作者信息

Mori Y, Mori T, Yoshida H, Ueda S, Iesato K, Wakashin Y, Wakashin M, Okuda K

出版信息

Clin Exp Immunol. 1984 Jul;57(1):85-92.

PMID:6430615
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1536088/
Abstract

This study was undertaken to produce experimental autoimmune hepatitis in mice, and to examine the role of liver specific lipoprotein (LSP), if any, and of cellular immunity in such a model. After immunization of three strains of mice (C57BL/6, C3H/He and BALB/c) with syngeneic crude liver proteins, most prominent liver changes histologically mimicking human hepatitis were produced in the liver of C57BL/6 (B6) mice. Antigenic and immunogenic activity of LSP in the crude liver proteins was decreased by the treatment of freezing and thawing, and the recovery of the antigenic activity seemed to correlate with the susceptibility of immunized mice to the induction of liver damage. Autoantibody against LSP was demonstrated in the serum of immunized B6 mice, but not in the sera of other strains after immunization. It was also found that EDTA contained in the buffer used for purification of LSP distinctly suppressed lymphocyte activity in vivo and in vitro. With the use of EDTA free LSP, it was shown that spleen cells of immunized B6 mice (especially of T cell enriched fraction) had a high reactivity studied by lymphocyte transformation test. Further examination showed that EDTA free LSP could induce mild liver lesions and lymphocyte reactivity against LSP, although neither histological change nor lymphocyte reactivity was found in the liver of B6 mice immunized with EDTA containing LSP.

摘要

本研究旨在诱导小鼠实验性自身免疫性肝炎,并在此模型中研究肝特异性脂蛋白(LSP)(若存在)及细胞免疫的作用。用同基因粗制肝蛋白免疫三种品系的小鼠(C57BL/6、C3H/He和BALB/c)后,C57BL/6(B6)小鼠肝脏出现了最显著的组织学变化,类似于人类肝炎。粗制肝蛋白中LSP的抗原性和免疫原性活性经冻融处理后降低,抗原活性的恢复似乎与免疫小鼠对肝损伤诱导的易感性相关。免疫后的B6小鼠血清中可检测到抗LSP自身抗体,而其他品系免疫后血清中未检测到。还发现,用于纯化LSP的缓冲液中所含的EDTA在体内和体外均能明显抑制淋巴细胞活性。使用不含EDTA的LSP时,通过淋巴细胞转化试验研究发现,免疫后的B6小鼠脾细胞(尤其是富含T细胞的部分)具有高反应性。进一步研究表明,不含EDTA的LSP可诱导轻度肝损伤以及针对LSP的淋巴细胞反应,而用含EDTA的LSP免疫的B6小鼠肝脏中未发现组织学变化和淋巴细胞反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c125/1536088/09c54cc9c706/clinexpimmunol00142-0100-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c125/1536088/9a29f3a4dd0a/clinexpimmunol00142-0099-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c125/1536088/a4698efa6d32/clinexpimmunol00142-0098-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c125/1536088/09c54cc9c706/clinexpimmunol00142-0100-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c125/1536088/9a29f3a4dd0a/clinexpimmunol00142-0099-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c125/1536088/a4698efa6d32/clinexpimmunol00142-0098-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c125/1536088/09c54cc9c706/clinexpimmunol00142-0100-a.jpg

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本文引用的文献

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Histological and immunological investigation of liver-specific protein (LSP) immunized rabbits compared with patients with liver disease.将肝特异性蛋白(LSP)免疫的兔子与肝病患者进行比较的组织学和免疫学研究。
Clin Exp Immunol. 1981 Jul;45(1):143-51.
2
Immune response to rabbit liver-specific lipoprotein in acute viral hepatitis.急性病毒性肝炎中对兔肝特异性脂蛋白的免疫反应。
Clin Exp Immunol. 1980 Dec;42(3):436-40.
3
Autoantibody responses to liver-specific lipoprotein in mice.小鼠对肝脏特异性脂蛋白的自身抗体反应。
髓质胸腺上皮细胞与自身免疫性肝炎发生中的中枢耐受:来自一种新小鼠模型的新视角
Int J Mol Sci. 2015 Jan 16;16(1):1980-2000. doi: 10.3390/ijms16011980.
4
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Int J Exp Pathol. 2014 Oct;95(5):309-20. doi: 10.1111/iep.12090. Epub 2014 Aug 12.
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Autoimmune hepatitis-like disease in C57BL/6 mice infected with mouse hepatitis virus A59.感染鼠肝炎病毒 A59 的 C57BL/6 小鼠中的自身免疫性肝炎样疾病。
Int Immunopharmacol. 2011 Oct;11(10):1591-8. doi: 10.1016/j.intimp.2011.05.020. Epub 2011 May 31.
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The autoimmune response induced by mouse hepatitis virus A59 is expanded by a hepatotoxic agent.由鼠肝炎病毒 A59 引起的自身免疫反应可被肝毒性物质所扩大。
Int Immunopharmacol. 2009 May;9(5):627-31. doi: 10.1016/j.intimp.2009.02.006. Epub 2009 Mar 1.
7
Chronic active hepatitis in transgenic mice expressing interferon-gamma in the liver.肝脏中表达γ干扰素的转基因小鼠的慢性活动性肝炎
Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):614-8. doi: 10.1073/pnas.91.2.614.
8
Study of cellular immunity in experimental autoimmune hepatitis in mice: transfer of spleen cells sensitized with liver proteins.小鼠实验性自身免疫性肝炎的细胞免疫研究:用肝脏蛋白致敏的脾细胞转移
Clin Exp Immunol. 1985 Sep;61(3):577-84.
9
Effect of neonatal thymectomy on experimental autoimmune hepatitis in mice.新生期胸腺切除对小鼠实验性自身免疫性肝炎的影响。
Clin Exp Immunol. 1987 Jan;67(1):105-13.
10
Studies on the pathogenesis of murine experimental autoimmune active hepatitis: sensitized T cell involvement in its induction.小鼠实验性自身免疫性活动性肝炎发病机制的研究:致敏T细胞参与其诱导过程。
Clin Exp Immunol. 1987 Feb;67(2):326-34.
Immunology. 1981 Jun;43(2):219-26.
4
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Klin Wochenschr. 1981 Jun 15;59(12):669-74. doi: 10.1007/BF02593858.
5
Detection and characterization of liver membrane autoantibodies in chronic active hepatitis by a solid-phase radioimmunoassay.用固相放射免疫分析法检测慢性活动性肝炎患者肝细胞膜自身抗体并进行特性分析。
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