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The Expression of PD-1 Ligands and Their Involvement in Regulation of T Cell Functions in Acute and Chronic Woodchuck Hepatitis Virus Infection
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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3194835/ https://www.ncbi.nlm.nih.gov/pubmed/22022563 http://dx.doi.org/10.1371/journal.pone.0026196 |
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author | Zhang, Ejuan Zhang, Xiaoyong Liu, Jia Wang, Baoju Tian, Yongjun Kosinska, Anna D. Ma, Zhiyong Xu, Yang Dittmer, Ulf Roggendorf, Michael Yang, Dongliang Lu, Mengji |
author_facet | Zhang, Ejuan Zhang, Xiaoyong Liu, Jia Wang, Baoju Tian, Yongjun Kosinska, Anna D. Ma, Zhiyong Xu, Yang Dittmer, Ulf Roggendorf, Michael Yang, Dongliang Lu, Mengji |
author_sort | Zhang, Ejuan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3194835 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31948352011-10-21 The Expression of PD-1 Ligands and Their Involvement in Regulation of T Cell Functions in Acute and Chronic Woodchuck Hepatitis Virus Infection Zhang, Ejuan Zhang, Xiaoyong Liu, Jia Wang, Baoju Tian, Yongjun Kosinska, Anna D. Ma, Zhiyong Xu, Yang Dittmer, Ulf Roggendorf, Michael Yang, Dongliang Lu, Mengji PLoS One Research Article 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. Public Library of Science 2011-10-14 /pmc/articles/PMC3194835/ /pubmed/22022563 http://dx.doi.org/10.1371/journal.pone.0026196 Text en Zhang et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Zhang, Ejuan Zhang, Xiaoyong Liu, Jia Wang, Baoju Tian, Yongjun Kosinska, Anna D. Ma, Zhiyong Xu, Yang Dittmer, Ulf Roggendorf, Michael Yang, Dongliang Lu, Mengji The Expression of PD-1 Ligands and Their Involvement in Regulation of T Cell Functions in Acute and Chronic Woodchuck Hepatitis Virus Infection |
title | The Expression of PD-1 Ligands and Their Involvement in Regulation of T Cell Functions in Acute and Chronic Woodchuck Hepatitis Virus Infection |
title_full | The Expression of PD-1 Ligands and Their Involvement in Regulation of T Cell Functions in Acute and Chronic Woodchuck Hepatitis Virus Infection |
title_fullStr | The Expression of PD-1 Ligands and Their Involvement in Regulation of T Cell Functions in Acute and Chronic Woodchuck Hepatitis Virus Infection |
title_full_unstemmed | The Expression of PD-1 Ligands and Their Involvement in Regulation of T Cell Functions in Acute and Chronic Woodchuck Hepatitis Virus Infection |
title_short | The Expression of PD-1 Ligands and Their Involvement in Regulation of T Cell Functions in Acute and Chronic Woodchuck Hepatitis Virus Infection |
title_sort | expression of pd-1 ligands and their involvement in regulation of t cell functions in acute and chronic woodchuck hepatitis virus infection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3194835/ https://www.ncbi.nlm.nih.gov/pubmed/22022563 http://dx.doi.org/10.1371/journal.pone.0026196 |
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