Mühlbauer Marcus, Fleck Martin, Schütz Christian, Weiss Thomas, Froh Matthias, Blank Christian, Schölmerich Jürgen, Hellerbrand Claus
Department of Internal Medicine I, University of Regensburg, D-93042 Regensburg, Germany.
J Hepatol. 2006 Oct;45(4):520-8. doi: 10.1016/j.jhep.2006.05.007. Epub 2006 Jun 16.
BACKGROUND/AIMS: B7-H1 (PD-L1) is a B7-family member that binds to programmed death-1 (PD-1). Recently, deficiency of PD-L1 has been demonstrated to result in accelerated hepatocyte damage in experimental autoimmune hepatitis, and PD-L1 was suggested to play a critical role in regulating T cell homeostasis. Absence of PD-1 enhanced proliferation of T cells in adenovirus-infected livers and resulted in a rapid clearance of the virus. Here, we aimed to get more insight into hepatic PD-L1 expression, regulation and function.
PD-L1 expression was analyzed by quantitative PCR and FACS-analysis in primary human liver cells and hepatoma cells. Furthermore, coculture experiments with primary human T cells or Jurkat T cells were established.
In addition to nonparenchymal liver cells, also hepatocytes constitutively expressed low levels of PD-L1. PD-L1 expression in hepatocytes was strongly enhanced by activated T cells and viral infection, and markedly augmented by further stimulation with type I or type II interferons. Moreover, PD-L1 expression on hepatocytes induced apoptosis in T cells.
Our results suggest a novel bidirectional interaction between hepatocytes and lymphocytes modulated by PD-L1 expression in hepatocytes, which may contribute to the unique immunological properties of the liver.
背景/目的：B7-H1（程序性死亡配体1，PD-L1）是一种B7家族成员，可与程序性死亡受体1（PD-1）结合。最近的研究表明，在实验性自身免疫性肝炎中，PD-L1缺乏会导致肝细胞损伤加速，提示PD-L1在调节T细胞稳态中起关键作用。在腺病毒感染的肝脏中，PD-1缺失会增强T细胞增殖，并导致病毒快速清除。在此，我们旨在更深入地了解肝脏中PD-L1的表达、调控及功能。
采用定量PCR和流式细胞术分析原代人肝细胞和肝癌细胞中PD-L1的表达。此外，还建立了原代人T细胞或Jurkat T细胞的共培养实验。
除了非实质肝细胞外，肝细胞也组成性表达低水平的PD-L1。活化的T细胞和病毒感染可显著增强肝细胞中PD-L1的表达，而Ⅰ型或Ⅱ型干扰素的进一步刺激则可使其明显上调。此外，肝细胞上的PD-L1表达可诱导T细胞凋亡。
我们的结果提示，肝细胞与淋巴细胞之间存在一种由肝细胞中PD-L1表达调节的新型双向相互作用，这可能有助于肝脏独特的免疫特性。
