Cross-presentation of antigen by diverse subsets of murine liver cells.

Cross-presentation of antigen by diverse subsets of murine liver cells.
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DOI:
10.1002/hep.24508
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发表时间:
2011-10
期刊:
影响因子:
13.5
通讯作者:
Crispe, Ian N.
Crispe, Ian N.
中科院分区:
医学1区
文献类型:
--
作者:
Ebrahimkhani, Mohammad R.;Mohar, Isaac;Crispe, Ian N.

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抗原交叉呈递是骨髓来源的专门抗原呈递细胞(例如树突状细胞)的主要功能。虽然这些细胞有时被称为“专业”抗原呈递细胞,但非骨髓来源的细胞也可以充当抗原呈递细胞。在这里,通过四路肝细胞分离和候选抗原呈递细胞的平行比较,我们表明,根据抗原供体细胞的丰度,不同的肝细胞亚群可以交叉呈递肝细胞相关抗原。即使在非常低的抗原浓度以及使用可溶性蛋白时,在肝窦内皮细胞和库普弗细胞中也观察到这种功能。肝细胞的抗原交叉呈递诱导有效的 CD8+ T 细胞增殖,其方式与来自脾脏的经典树突状细胞类似。然而,增殖细胞表达较低水平的 T 细胞激活标记物和细胞内干扰素-γ 水平。与经典的脾树突状细胞相反,肝脏抗原呈递细胞的交叉呈递主要依赖于细胞间粘附分子-1。肝窦是一个富含抗原交叉呈递活性的环境。然而,肝脏中常驻的抗原呈递细胞会导致部分 T 细胞激活。这些结果阐明了肝脏如何作为 CD8+ T 细胞激活的主要部位,以及为什么针对肝细胞病原体的免疫有时无效
Antigen cross-presentation is a principal function of specialized antigen-presenting cells of bone marrow origin such as dendritic cells. While these cells are sometimes known as “professional” antigen-presenting cells, non-bone marrow derived cells may also act as antigen-presenting cells. Here, using four-way liver cell isolation and parallel comparison of candidate antigen presenting cells, we show that depending on the abundance of antigen-donor cells, different subsets of liver cells could cross-present a hepatocyte-associated antigen. This function was observed in both liver sinusoidal endothelial cells and Kupffer cells even at very low antigen concentration, as well as when using soluble protein. Antigen cross-presentation by liver cells induced efficient CD8+ T cell proliferation in a similar manner to classical dendritic cells from spleen. However, proliferated cells expressed lower level of T-cell activation markers and intracellular interferon-gamma levels. In contrast to classical spleen dendritic cells, cross-presentation by liver antigen presenting cells was predominantly dependent on Intercellular Adhesion Molecule-1. Hepatic sinusoids are an environment rich in antigen cross-presenting activity. However the liver's resident antigen-presenting cells cause partial T-cell activation. These results clarify how the liver can act as a primary site of CD8+ T-cell activation, and why immunity against hepatocyte pathogens is sometimes ineffective
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