PD-L1 is induced in hepatocytes by viral infection and by interferon-alpha and -gamma and mediates T cell apoptosis.
OBJECTIVE
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.
Mühlbauer
Marcus
M
Department of Internal Medicine I, University of Regensburg, D-93042 Regensburg, Germany.
Fleck
Martin
M
Schütz
Christian
C
Weiss
Thomas
T
Froh
Matthias
M
Blank
Christian
C
Schölmerich
Jürgen
J
Hellerbrand
Claus
C
D000258:Adenovirus Infections, Human / Q000276:immunology*; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000276:immunology*; D060890:B7-H1 Antigen; D002450:Cell Communication / Q000276:immunology; D018920:Coculture Techniques; D015870:Gene Expression / Q000276:immunology; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D019169:Jurkat Cells; D008099:Liver / Q000166:cytology / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000821:virology*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D016898:Interferon-alpha; D012333:RNA, Messenger; D007371:Interferon-gamma