原发性胆汁性肝硬化的细胞免疫学发病机制

王寅虎; 杨微; M.Eric Gershwin; 廉哲雄

原发性胆汁性肝硬化的细胞免疫学发病机制

1. 中国科学技术大学生命科学学院肝脏免疫学实验室
2. 加利福尼亚大学戴维斯分校

详细信息

中图分类号: R575.2
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出版历程
- 出版日期: 2011-06-20

Cellular mechanism of immunopathogenesis of primary biliary cirrhosis

摘要

摘要: 原发性胆汁性肝硬化（PBC）是一种器官特异性的进行性自身免疫疾病,常见于女性,以肝脏门脉周围的淋巴细胞浸润,胆管上皮细胞特异性损伤以及血清中高滴度抗线粒体抗体（AMA）为主要特征。最新的PBC研究采用了CD4启动子控制下的TGFβ受体2显性失活（dnTGFβRⅡ）小鼠模型,这种小鼠模型很好地模拟了PBC患者的典型特征。在这种小鼠的基因背景下,通过分别敲除Rag1,μ以及CD1d基因建立了多种双基因缺陷鼠,通过研究发现T细胞,B细胞以及CD1d限制的NKT细胞等对肝脏淋巴细胞浸润,胆管上皮细胞损伤以及AMA的产生发挥着重要的作用。一系列的细胞免疫学实验结果显示,是CD8+T细胞而非CD4+T细胞在肝脏损伤过程中起着决定性的作用,而B细胞除分泌抗自身抗体之外,还具有抑制PBC发生的免疫调节作用。这些机制的研究为揭示人类PBC疾病的细胞免疫学致病机理提供了有力的证据和依托。
- 肝硬化,胆汁性 /
- 疾病模型,动物 /
- 杀伤细胞,天然 /
- B淋巴细胞 /
- T淋巴细胞
Abstract: Primary biliary cirrhosis (PBC) is a progressive, organ-specific autoimmune disease that predominantly affects woman and is characterized by lymphocytic infiltration in portal tracts, immune-mediated destruction of small intrahepatic small bile ducts, and the presence of high titers of serum anti-mitochondrial Abs (AMAs) .A murine model of PBC, generated by expressing a dominant-negative form of TGFβ receptor type Ⅱ (dnTGFβRⅡ) under the direction of the CD4 promoter, demonstrates several key features of human PBC and has been applied in previous PBC studies.Experimental data from Rag1-/-, μ-/-and CD1d-/-mice on a dnTGFβRⅡ background indicated that T cells, B cells and CD1d-restricted NKT cells plays critical roles in liver injury.Moreover, based on a rigorous series of cellular immunological studies, it is concluded that CD8+, but not CD4+ T cells, play a prominent role in mediating pathogenesis, and that B cells can have a suppressive regulatory effect on the infiammatory response besides just secreting auto-antibodies.These studies provide substantial evidence for a cellular mechanism in human primary biliary cirrhosis pathogenesis.
- liver cirrhosis /
- biliary /
- disease models /
- animal /
- killer cells

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参考文献(21)

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