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Liver Is Able to Activate Naïve CD8(+) T Cells with Dysfunctional Anti-Viral Activity in the Murine System
The liver possesses distinct tolerogenic properties because of continuous exposure to bacterial constituents and nonpathogenic food antigen. The central immune mediators required for the generation of effective immune responses in the liver environment have not been fully elucidated. In this report,...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764869/ https://www.ncbi.nlm.nih.gov/pubmed/19876399 http://dx.doi.org/10.1371/journal.pone.0007619 |
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author | Lukens, John R. Dolina, Joseph S. Kim, Taeg S. Tacke, Robert S. Hahn, Young S. |
author_facet | Lukens, John R. Dolina, Joseph S. Kim, Taeg S. Tacke, Robert S. Hahn, Young S. |
author_sort | Lukens, John R. |
collection | PubMed |
description | The liver possesses distinct tolerogenic properties because of continuous exposure to bacterial constituents and nonpathogenic food antigen. The central immune mediators required for the generation of effective immune responses in the liver environment have not been fully elucidated. In this report, we demonstrate that the liver can indeed support effector CD8(+) T cells during adenovirus infection when the T cells are primed in secondary lymphoid tissues. In contrast, when viral antigen is delivered predominantly to the liver via intravenous (IV) adenovirus infection, intrahepatic CD8(+) T cells are significantly impaired in their ability to produce inflammatory cytokines and lyse target cells. Additionally, intrahepatic CD8(+) T cells generated during IV adenovirus infection express elevated levels of PD-1. Notably, lower doses of adenovirus infection do not rescue the impaired effector function of intrahepatic CD8(+) T cell responses. Instead, intrahepatic antigen recognition limits the generation of potent anti-viral responses at both priming and effector stages of the CD8(+) T cell response and accounts for the dysfunctional CD8(+) T cell response observed during IV adenovirus infection. These results also implicate that manipulation of antigen delivery will facilitate the design of improved vaccination strategies to persistent viral infection. |
format | Text |
id | pubmed-2764869 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-27648692009-10-30 Liver Is Able to Activate Naïve CD8(+) T Cells with Dysfunctional Anti-Viral Activity in the Murine System Lukens, John R. Dolina, Joseph S. Kim, Taeg S. Tacke, Robert S. Hahn, Young S. PLoS One Research Article The liver possesses distinct tolerogenic properties because of continuous exposure to bacterial constituents and nonpathogenic food antigen. The central immune mediators required for the generation of effective immune responses in the liver environment have not been fully elucidated. In this report, we demonstrate that the liver can indeed support effector CD8(+) T cells during adenovirus infection when the T cells are primed in secondary lymphoid tissues. In contrast, when viral antigen is delivered predominantly to the liver via intravenous (IV) adenovirus infection, intrahepatic CD8(+) T cells are significantly impaired in their ability to produce inflammatory cytokines and lyse target cells. Additionally, intrahepatic CD8(+) T cells generated during IV adenovirus infection express elevated levels of PD-1. Notably, lower doses of adenovirus infection do not rescue the impaired effector function of intrahepatic CD8(+) T cell responses. Instead, intrahepatic antigen recognition limits the generation of potent anti-viral responses at both priming and effector stages of the CD8(+) T cell response and accounts for the dysfunctional CD8(+) T cell response observed during IV adenovirus infection. These results also implicate that manipulation of antigen delivery will facilitate the design of improved vaccination strategies to persistent viral infection. Public Library of Science 2009-10-30 /pmc/articles/PMC2764869/ /pubmed/19876399 http://dx.doi.org/10.1371/journal.pone.0007619 Text en Lukens 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 Lukens, John R. Dolina, Joseph S. Kim, Taeg S. Tacke, Robert S. Hahn, Young S. Liver Is Able to Activate Naïve CD8(+) T Cells with Dysfunctional Anti-Viral Activity in the Murine System |
title | Liver Is Able to Activate Naïve CD8(+) T Cells with Dysfunctional Anti-Viral Activity in the Murine System |
title_full | Liver Is Able to Activate Naïve CD8(+) T Cells with Dysfunctional Anti-Viral Activity in the Murine System |
title_fullStr | Liver Is Able to Activate Naïve CD8(+) T Cells with Dysfunctional Anti-Viral Activity in the Murine System |
title_full_unstemmed | Liver Is Able to Activate Naïve CD8(+) T Cells with Dysfunctional Anti-Viral Activity in the Murine System |
title_short | Liver Is Able to Activate Naïve CD8(+) T Cells with Dysfunctional Anti-Viral Activity in the Murine System |
title_sort | liver is able to activate naïve cd8(+) t cells with dysfunctional anti-viral activity in the murine system |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764869/ https://www.ncbi.nlm.nih.gov/pubmed/19876399 http://dx.doi.org/10.1371/journal.pone.0007619 |
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