PD-L1 Is Induced in Hepatocytes by Viral Infection and by Interferon-Alpha and -Gamma and Mediates T Cell Apoptosis

J Hepatol. 2006 Oct;45(4):520-8. doi: 10.1016/j.jhep.2006.05.007. Epub 2006 Jun 16.

Abstract

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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenovirus Infections, Human / immunology*
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Apoptosis / immunology*
  • B7-H1 Antigen
  • Cell Communication / immunology
  • Coculture Techniques
  • Gene Expression / immunology
  • Hepatocytes / cytology
  • Hepatocytes / metabolism
  • Hepatocytes / virology*
  • Humans
  • Interferon-alpha / metabolism
  • Interferon-gamma / metabolism
  • Jurkat Cells
  • Liver / cytology
  • Liver / immunology
  • Liver / virology
  • Lymphocyte Activation / immunology
  • RNA, Messenger / analysis
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / virology*
  • Tumor Cells, Cultured

Substances

  • Antigens, CD
  • B7-H1 Antigen
  • CD274 protein, human
  • Interferon-alpha
  • RNA, Messenger
  • Interferon-gamma