1. The expression of PD-1 ligands and their involvement in regulation of T cell functions in acute and chronic woodchuck hepatitis virus infection
- Author
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Ejuan Zhang, Zhiyong Ma, Mengji Lu, Ulf Dittmer, Baoju Wang, Xiaoyong Zhang, Michael Roggendorf, Dongliang Yang, Anna D. Kosinska, Yang Xu, Jia Liu, and Yongjun Tian
- Subjects
Gastroenterology and hepatology ,viruses ,T-Lymphocytes ,Medizin ,lcsh:Medicine ,medicine.disease_cause ,Ligands ,B7-H1 Antigen ,Cell Degranulation ,Hepatitis ,Antibody Specificity ,Hepatitis B Virus, Woodchuck ,Cloning, Molecular ,Receptor ,lcsh:Science ,Cells, Cultured ,Phylogeny ,Multidisciplinary ,medicine.diagnostic_test ,T Cells ,Woodchuck hepatitis virus ,Toll-Like Receptors ,Hepatitis B ,Infectious hepatitis ,medicine.anatomical_structure ,Acute Disease ,Medicine ,Infectious diseases ,Antibody ,Research Article ,T cell ,Immune Cells ,Molecular Sequence Data ,Immunology ,Viral diseases ,Biology ,Peripheral blood mononuclear cell ,Flow cytometry ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Liver diseases ,Cell Proliferation ,Hepatitis B virus ,lcsh:R ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,Programmed Cell Death 1 Ligand 2 Protein ,Virology ,digestive system diseases ,Chronic infection ,Marmota ,Chronic Disease ,biology.protein ,Hepatocytes ,lcsh:Q ,Clinical Immunology ,Interferons ,Infectious Disease Modeling ,Sequence Alignment - Abstract
Background: The programmed cell death 1 (PD-1)/programmed death-1 ligand 1 (PD-L1) system may play a role in the negative regulation of T cell functions in hepatitis B virus (HBV) infection. Thus, it is important to study its role in the widely used animal model for HBV infection of woodchucks with woodchuck hepatitis virus (WHV). Methods: Woodchuck PD-L1 (wPD-L1) and -L2 (wPD-L2) were cloned and characterized. The levels of wPD-L1 expression in primary woodchuck hepatocytes (PWH), peripheral blood mononuclear cells (PBMCs), and liver tissue of naive and WHV-infected woodchucks were examined by real time reverse transcription (RT)-PCR and flow cytometry. Using antibodies against wPD-L1 and -L2, the effect of blocking PD-1/PD-L1/PD-L2 interaction on the proliferation and degranulation of woodchuck PBMCs was examined. Principal Findings: Both wPD-L1 and -L2 showed a high homology to their counterparts of other mammalian species and humans. WPD-L1 expression in PWH and PBMCs of naive animals was low but could be stimulated by Toll-like receptor (TLR) ligands and interferons (IFN). WPD-L1 expression in liver tissue was significantly higher than that measured in PWHs and was slightly elevated during acute and chronic WHV infection. However, wPD-1 and wPD-L1 expression on PBMCs was strongly up-regulated during acute and chronic infection. In vitro blockade with antibodies against wPD-L1 and -L2 partially enhanced proliferation and degranulation of PBMCs from WHV-infected woodchucks. Conclusions: Our results demonstrated that wPD-1/wPD-L1 expression in hepatocytes and PBMCs can be induced by different inflammatory stimuli and is up-regulated mainly on PBMCs during WHV infection. A blockade of the woodchuck PD-1/PD-L pathway could partially enhance T cell functions in WHV infection. © 2011 Zhang et al.
- Published
- 2011