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Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection
The inflamed liver in chronic hepatitis B virus (HBV) infection (CHB) is characterized by a large influx of non–virus-specific CD8 T cells. Little is known about the functional capacity of these lymphocytes, which could provide insights into mechanisms of failure of viral control and liver damage in...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2526205/ https://www.ncbi.nlm.nih.gov/pubmed/18695005 http://dx.doi.org/10.1084/jem.20072076 |
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author | Das, Abhishek Hoare, Matthew Davies, Nathan Lopes, A. Ross Dunn, Claire Kennedy, Patrick T.F. Alexander, Graeme Finney, Helene Lawson, Alistair Plunkett, Fiona J. Bertoletti, Antonio Akbar, Arne N. Maini, Mala K. |
author_facet | Das, Abhishek Hoare, Matthew Davies, Nathan Lopes, A. Ross Dunn, Claire Kennedy, Patrick T.F. Alexander, Graeme Finney, Helene Lawson, Alistair Plunkett, Fiona J. Bertoletti, Antonio Akbar, Arne N. Maini, Mala K. |
author_sort | Das, Abhishek |
collection | PubMed |
description | The inflamed liver in chronic hepatitis B virus (HBV) infection (CHB) is characterized by a large influx of non–virus-specific CD8 T cells. Little is known about the functional capacity of these lymphocytes, which could provide insights into mechanisms of failure of viral control and liver damage in this setting. We compared the effector function of total circulating and intrahepatic CD8 T cells in CHB patients and healthy donors. We demonstrated that CD8 T cells from CHB patients, regardless of their antigen specificity, were impaired in their ability to produce interleukin-2 and proliferate upon TCR-dependent stimulation. In contrast, these CD8 T cells had preserved production of the proinflammatory cytokines interferon-γ and tumor necrosis factor-α. This aberrant functional profile was partially attributable to down-regulation of the proximal T cell receptor signaling molecule CD3ζ, and could be corrected in vitro by transfection of CD3ζ or replenishment of the amino acid arginine required for its expression. We provide evidence for depletion of arginine in the inflamed hepatic microenvironment as a potential mechanism for these defects in global CD8 T cell signaling and function. These data imply that polarized CD8 T cells within the HBV-infected liver may impede proliferative antiviral effector function, while contributing to the proinflammatory cytokine environment. |
format | Text |
id | pubmed-2526205 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-25262052009-03-01 Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection Das, Abhishek Hoare, Matthew Davies, Nathan Lopes, A. Ross Dunn, Claire Kennedy, Patrick T.F. Alexander, Graeme Finney, Helene Lawson, Alistair Plunkett, Fiona J. Bertoletti, Antonio Akbar, Arne N. Maini, Mala K. J Exp Med Articles The inflamed liver in chronic hepatitis B virus (HBV) infection (CHB) is characterized by a large influx of non–virus-specific CD8 T cells. Little is known about the functional capacity of these lymphocytes, which could provide insights into mechanisms of failure of viral control and liver damage in this setting. We compared the effector function of total circulating and intrahepatic CD8 T cells in CHB patients and healthy donors. We demonstrated that CD8 T cells from CHB patients, regardless of their antigen specificity, were impaired in their ability to produce interleukin-2 and proliferate upon TCR-dependent stimulation. In contrast, these CD8 T cells had preserved production of the proinflammatory cytokines interferon-γ and tumor necrosis factor-α. This aberrant functional profile was partially attributable to down-regulation of the proximal T cell receptor signaling molecule CD3ζ, and could be corrected in vitro by transfection of CD3ζ or replenishment of the amino acid arginine required for its expression. We provide evidence for depletion of arginine in the inflamed hepatic microenvironment as a potential mechanism for these defects in global CD8 T cell signaling and function. These data imply that polarized CD8 T cells within the HBV-infected liver may impede proliferative antiviral effector function, while contributing to the proinflammatory cytokine environment. The Rockefeller University Press 2008-09-01 /pmc/articles/PMC2526205/ /pubmed/18695005 http://dx.doi.org/10.1084/jem.20072076 Text en © 2008 Das et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Articles Das, Abhishek Hoare, Matthew Davies, Nathan Lopes, A. Ross Dunn, Claire Kennedy, Patrick T.F. Alexander, Graeme Finney, Helene Lawson, Alistair Plunkett, Fiona J. Bertoletti, Antonio Akbar, Arne N. Maini, Mala K. Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection |
title | Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection |
title_full | Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection |
title_fullStr | Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection |
title_full_unstemmed | Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection |
title_short | Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection |
title_sort | functional skewing of the global cd8 t cell population in chronic hepatitis b virus infection |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2526205/ https://www.ncbi.nlm.nih.gov/pubmed/18695005 http://dx.doi.org/10.1084/jem.20072076 |
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