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Liver-primed CD8(+) T cells suppress antiviral adaptive immunity through galectin-9-independent T-Cell immunoglobulin and mucin 3 engagement of high-mobility group box 1 in mice

The liver is a tolerogenic environment exploited by persistent infections, such as hepatitis B (HBV) and C (HCV) viruses. In a murine model of intravenous hepatotropic adenovirus infection, liver-primed antiviral CD8(+) T cells fail to produce proinflammatory cytokines and do not display cytolytic a...

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Autores principales: Dolina, Joseph S, Braciale, Thomas J, Hahn, Young S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3970181/
https://www.ncbi.nlm.nih.gov/pubmed/24677194
http://dx.doi.org/10.1002/hep.26938
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author Dolina, Joseph S
Braciale, Thomas J
Hahn, Young S
author_facet Dolina, Joseph S
Braciale, Thomas J
Hahn, Young S
author_sort Dolina, Joseph S
collection PubMed
description The liver is a tolerogenic environment exploited by persistent infections, such as hepatitis B (HBV) and C (HCV) viruses. In a murine model of intravenous hepatotropic adenovirus infection, liver-primed antiviral CD8(+) T cells fail to produce proinflammatory cytokines and do not display cytolytic activity characteristic of effector CD8(+) T cells generated by infection at an extrahepatic, that is, subcutaneous, site. Importantly, liver-generated CD8(+) T cells also appear to have a T-regulatory (T(reg)) cell function exemplified by their ability to limit proliferation of antigen-specific T-effector (T(eff)) cells in vitro and in vivo via T-cell immunoglobulin and mucin 3 (Tim-3) expressed by the CD8(+) T(reg) cells. Regulatory activity did not require recognition of the canonical Tim-3 ligand, galectin-9, but was dependent on CD8(+) T(reg) cell-surface Tim-3 binding to the alarmin, high-mobility group box 1 (HMGB-1). Conclusion: Virus-specific Tim-3(+)CD8(+) T cells operating through HMGB-1 recognition in the setting of acute and chronic viral infections of the liver may act to dampen hepatic T-cell responses in the liver microenvironment and, as a consequence, limit immune-mediated tissue injury or promote the establishment of persistent infections. (Hepatology 2014;59:1351-1365)
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spelling pubmed-39701812014-12-11 Liver-primed CD8(+) T cells suppress antiviral adaptive immunity through galectin-9-independent T-Cell immunoglobulin and mucin 3 engagement of high-mobility group box 1 in mice Dolina, Joseph S Braciale, Thomas J Hahn, Young S Hepatology Viral Hepatitis The liver is a tolerogenic environment exploited by persistent infections, such as hepatitis B (HBV) and C (HCV) viruses. In a murine model of intravenous hepatotropic adenovirus infection, liver-primed antiviral CD8(+) T cells fail to produce proinflammatory cytokines and do not display cytolytic activity characteristic of effector CD8(+) T cells generated by infection at an extrahepatic, that is, subcutaneous, site. Importantly, liver-generated CD8(+) T cells also appear to have a T-regulatory (T(reg)) cell function exemplified by their ability to limit proliferation of antigen-specific T-effector (T(eff)) cells in vitro and in vivo via T-cell immunoglobulin and mucin 3 (Tim-3) expressed by the CD8(+) T(reg) cells. Regulatory activity did not require recognition of the canonical Tim-3 ligand, galectin-9, but was dependent on CD8(+) T(reg) cell-surface Tim-3 binding to the alarmin, high-mobility group box 1 (HMGB-1). Conclusion: Virus-specific Tim-3(+)CD8(+) T cells operating through HMGB-1 recognition in the setting of acute and chronic viral infections of the liver may act to dampen hepatic T-cell responses in the liver microenvironment and, as a consequence, limit immune-mediated tissue injury or promote the establishment of persistent infections. (Hepatology 2014;59:1351-1365) BlackWell Publishing Ltd 2014-04 2014-02-28 /pmc/articles/PMC3970181/ /pubmed/24677194 http://dx.doi.org/10.1002/hep.26938 Text en © 2014 The Authors. Hepatology published by Wiley on behalf of the American Association for the Study of Liver Diseases http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Viral Hepatitis
Dolina, Joseph S
Braciale, Thomas J
Hahn, Young S
Liver-primed CD8(+) T cells suppress antiviral adaptive immunity through galectin-9-independent T-Cell immunoglobulin and mucin 3 engagement of high-mobility group box 1 in mice
title Liver-primed CD8(+) T cells suppress antiviral adaptive immunity through galectin-9-independent T-Cell immunoglobulin and mucin 3 engagement of high-mobility group box 1 in mice
title_full Liver-primed CD8(+) T cells suppress antiviral adaptive immunity through galectin-9-independent T-Cell immunoglobulin and mucin 3 engagement of high-mobility group box 1 in mice
title_fullStr Liver-primed CD8(+) T cells suppress antiviral adaptive immunity through galectin-9-independent T-Cell immunoglobulin and mucin 3 engagement of high-mobility group box 1 in mice
title_full_unstemmed Liver-primed CD8(+) T cells suppress antiviral adaptive immunity through galectin-9-independent T-Cell immunoglobulin and mucin 3 engagement of high-mobility group box 1 in mice
title_short Liver-primed CD8(+) T cells suppress antiviral adaptive immunity through galectin-9-independent T-Cell immunoglobulin and mucin 3 engagement of high-mobility group box 1 in mice
title_sort liver-primed cd8(+) t cells suppress antiviral adaptive immunity through galectin-9-independent t-cell immunoglobulin and mucin 3 engagement of high-mobility group box 1 in mice
topic Viral Hepatitis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3970181/
https://www.ncbi.nlm.nih.gov/pubmed/24677194
http://dx.doi.org/10.1002/hep.26938
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