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HBV-Specific CD8+ T-Cell Tolerance in the Liver

Hepatitis B virus (HBV) remains a leading cause of liver-related morbidity and mortality through chronic hepatitis that may progress to liver cirrhosis and cancer. The central role played by HBV-specific CD8+ T cells in the clearance of acute HBV infection, and HBV-related liver injury is now well e...

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Autores principales: Baudi, Ian, Kawashima, Keigo, Isogawa, Masanori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378532/
https://www.ncbi.nlm.nih.gov/pubmed/34421926
http://dx.doi.org/10.3389/fimmu.2021.721975
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author Baudi, Ian
Kawashima, Keigo
Isogawa, Masanori
author_facet Baudi, Ian
Kawashima, Keigo
Isogawa, Masanori
author_sort Baudi, Ian
collection PubMed
description Hepatitis B virus (HBV) remains a leading cause of liver-related morbidity and mortality through chronic hepatitis that may progress to liver cirrhosis and cancer. The central role played by HBV-specific CD8+ T cells in the clearance of acute HBV infection, and HBV-related liver injury is now well established. Vigorous, multifunctional CD8+ T cell responses are usually induced in most adult-onset HBV infections, while chronic hepatitis B (CHB) is characterized by quantitatively and qualitatively weak HBV-specific CD8+ T cell responses. The molecular basis of this dichotomy is poorly understood. Genomic analysis of dysfunctional HBV-specific CD8+ T cells in CHB patients and various mouse models suggest that multifaceted mechanisms including negative signaling and metabolic abnormalities cooperatively establish CD8+ T cell dysfunction. Immunoregulatory cell populations in the liver, including liver resident dendritic cells (DCs), hepatic stellate cells (HSCs), myeloid-derived suppressor cells (MDSCs), may contribute to intrahepatic CD8+ T cell dysfunction through the production of soluble mediators, such as arginase, indoleamine 2,3-dioxygenase (IDO) and suppressive cytokines and the expression of co-inhibitory molecules. A series of recent studies with mouse models of HBV infection suggest that genetic and epigenetic changes in dysfunctional CD8+ T cells are the manifestation of prolonged antigenic stimulation, as well as the absence of co-stimulatory or cytokine signaling. These new findings may provide potential new targets for immunotherapy aiming at invigorating HBV-specific CD8+ T cells, which hopefully cures CHB.
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spelling pubmed-83785322021-08-21 HBV-Specific CD8+ T-Cell Tolerance in the Liver Baudi, Ian Kawashima, Keigo Isogawa, Masanori Front Immunol Immunology Hepatitis B virus (HBV) remains a leading cause of liver-related morbidity and mortality through chronic hepatitis that may progress to liver cirrhosis and cancer. The central role played by HBV-specific CD8+ T cells in the clearance of acute HBV infection, and HBV-related liver injury is now well established. Vigorous, multifunctional CD8+ T cell responses are usually induced in most adult-onset HBV infections, while chronic hepatitis B (CHB) is characterized by quantitatively and qualitatively weak HBV-specific CD8+ T cell responses. The molecular basis of this dichotomy is poorly understood. Genomic analysis of dysfunctional HBV-specific CD8+ T cells in CHB patients and various mouse models suggest that multifaceted mechanisms including negative signaling and metabolic abnormalities cooperatively establish CD8+ T cell dysfunction. Immunoregulatory cell populations in the liver, including liver resident dendritic cells (DCs), hepatic stellate cells (HSCs), myeloid-derived suppressor cells (MDSCs), may contribute to intrahepatic CD8+ T cell dysfunction through the production of soluble mediators, such as arginase, indoleamine 2,3-dioxygenase (IDO) and suppressive cytokines and the expression of co-inhibitory molecules. A series of recent studies with mouse models of HBV infection suggest that genetic and epigenetic changes in dysfunctional CD8+ T cells are the manifestation of prolonged antigenic stimulation, as well as the absence of co-stimulatory or cytokine signaling. These new findings may provide potential new targets for immunotherapy aiming at invigorating HBV-specific CD8+ T cells, which hopefully cures CHB. Frontiers Media S.A. 2021-08-06 /pmc/articles/PMC8378532/ /pubmed/34421926 http://dx.doi.org/10.3389/fimmu.2021.721975 Text en Copyright © 2021 Baudi, Kawashima and Isogawa https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Baudi, Ian
Kawashima, Keigo
Isogawa, Masanori
HBV-Specific CD8+ T-Cell Tolerance in the Liver
title HBV-Specific CD8+ T-Cell Tolerance in the Liver
title_full HBV-Specific CD8+ T-Cell Tolerance in the Liver
title_fullStr HBV-Specific CD8+ T-Cell Tolerance in the Liver
title_full_unstemmed HBV-Specific CD8+ T-Cell Tolerance in the Liver
title_short HBV-Specific CD8+ T-Cell Tolerance in the Liver
title_sort hbv-specific cd8+ t-cell tolerance in the liver
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378532/
https://www.ncbi.nlm.nih.gov/pubmed/34421926
http://dx.doi.org/10.3389/fimmu.2021.721975
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