Isolation and functional characteristics of liver dendritic cells

肝树突状细胞的分离及功能特性

基本信息

批准号：
12670494
负责人：
AKBAR S.m.f.
金额：
$ 1.79万
依托单位：
Ehime University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670494/
关键词：
Liver Diseases Liver dendritic cells Surface markers Cytokines Antigen presentation

项目摘要

Dendritic cells (DC) are the most potent professional antigen-presenting cells (APC). DC process and present antigen to naive T cells and also ensure the functioning and survival of activated lymphocytes. Although widely distributed in the body, the phenorype and function of DC differs according to their localization and levels of maturation. We showed that defective function of peripheral blood DC in patients with chronic hepatitis B and activation and maturation of peripheral blood DC during vaccine therapy. We also detected mature DC from the liver tissues from patients with chronic liver diseases and further showed a lack of mature DC at the liver tissue in hepatocellular carcinoma. However, it was not possible to isolate this trace population of APC from the human liver due to technical limitation.To over come this, we isolated liver DC from normal as well as from a mouse model of hepatitis. Liver DC from normal mouse showed an immature phenotype expressing very low levels of costimulatory molecules like CD40, CD80 and CD86. However, after encountering antigens, liver DC were capable of capturing, processing and presenting soluble antigens to T cells. Next, we checked whether the function of liver DC were compromised during inflammation of the liver. Experimental hepatitis was induced in C57BL/6 by injecting concanavalin A (Con A). Liver DC from mice with hepatitis could not induce proliferation of antigen-specific T cell and immune regulatory cytokines. The findings of impaired function of liver DC from mice with experimental acute hepatitis was further confirmed by studying the function of liver DC in a mouse model of chronic hepatitis.In summary, these studies indicate that impaired APC capacity of liver DC during hepatitis may underlie the impaired magnitude of antigen-specific immune response during hepatitis.

树突状细胞（DC）是最有效的专业抗原呈递细胞（APC）。 DC 处理并向初始 T 细胞呈递抗原，并确保活化淋巴细胞的功能和存活。尽管 DC 广泛分布于体内，但其表型和功能根据其定位和成熟水平而有所不同。我们发现慢性乙型肝炎患者外周血DC的功能缺陷以及疫苗治疗期间外周血DC的活化和成熟。我们还在慢性肝病患者的肝组织中检测到成熟DC，并进一步表明肝细胞癌的肝组织中缺乏成熟DC。然而，由于技术限制，不可能从人类肝脏中分离出微量 APC 群体。为了克服这个问题，我们从正常以及肝炎小鼠模型中分离出肝脏 DC。来自正常小鼠的肝脏 DC 显示出不成熟的表型，表达非常低水平的共刺激分子，如 CD40、CD80 和 CD86。然而，在遇到抗原后，肝脏 DC 能够捕获、加工并向 T 细胞呈递可溶性抗原。接下来，我们检查了肝脏炎症期间肝脏 DC 的功能是否受到损害。通过注射伴刀豆球蛋白 A (Con A) 在 C57BL/6 中诱导实验性肝炎。肝炎小鼠的肝 DC 不能诱导抗原特异性 T 细胞和免疫调节细胞因子的增殖。通过研究慢性肝炎小鼠模型中肝 DC 的功能，进一步证实了实验性急性肝炎小鼠肝 DC 功能受损的发现。总之，这些研究表明，肝炎期间肝 DC 的 APC 能力受损可能是导致肝炎发生的原因。肝炎期间抗原特异性免疫反应的强度受损。