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Improved Functionality of Exhausted Intrahepatic CXCR5+ CD8+ T Cells Contributes to Chronic Antigen Clearance Upon Immunomodulation

Chronic hepatotropic viral infections are characterized by exhausted CD8+ T cells in the presence of cognate antigen in the liver. The impairment of T cell response limits the control of chronic hepatotropic viruses. Immune-modulatory strategies are attractive options to re-invigorate exhausted T ce...

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Autores principales: Kumashie, Kingsley Gideon, Cebula, Marcin, Hagedorn, Claudia, Kreppel, Florian, Pils, Marina C., Koch-Nolte, Friedrich, Rissiek, Björn, Wirth, Dagmar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886981/
https://www.ncbi.nlm.nih.gov/pubmed/33613516
http://dx.doi.org/10.3389/fimmu.2020.592328
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author Kumashie, Kingsley Gideon
Cebula, Marcin
Hagedorn, Claudia
Kreppel, Florian
Pils, Marina C.
Koch-Nolte, Friedrich
Rissiek, Björn
Wirth, Dagmar
author_facet Kumashie, Kingsley Gideon
Cebula, Marcin
Hagedorn, Claudia
Kreppel, Florian
Pils, Marina C.
Koch-Nolte, Friedrich
Rissiek, Björn
Wirth, Dagmar
author_sort Kumashie, Kingsley Gideon
collection PubMed
description Chronic hepatotropic viral infections are characterized by exhausted CD8+ T cells in the presence of cognate antigen in the liver. The impairment of T cell response limits the control of chronic hepatotropic viruses. Immune-modulatory strategies are attractive options to re-invigorate exhausted T cells. However, in hepatotropic viral infections, the knowledge about immune-modulatory effects on the in-situ regulation of exhausted intrahepatic CD8+ T cells is limited. In this study, we elucidated the functional heterogeneity in the pool of exhausted CD8+ T cells in the liver of mice expressing the model antigen Ova in a fraction of hepatocytes. We found a subpopulation of intrahepatic CXCR5+ Ova-specific CD8+ T cells, which are profoundly cytotoxic, exhibiting efficient metabolic functions as well as improved memory recall and self-maintenance. The intrahepatic Ova-specific CXCR5+ CD8+ T cells are possibly tissue resident cells, which may rely largely on OXPHOS and glycolysis to fuel their cellular processes. Importantly, host conditioning with CpG oligonucleotide reinvigorates and promotes exhausted T cell expansion, facilitating complete antigen eradication. The CpG oligonucleotide-mediated reinvigoration may support resident memory T cell formation and the maintenance of CXCR5+ Ova-specific CD8+ T cells in the liver. These findings suggest that CpG oligodinucleotide may preferentially target CXCR5+ CD8+ T cells for expansion to facilitate the revival of exhausted T cells. Thus, therapeutic strategies aiming to expand CXCR5+ CD8+ T cells might provide a novel approach against chronic liver infection.
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spelling pubmed-78869812021-02-18 Improved Functionality of Exhausted Intrahepatic CXCR5+ CD8+ T Cells Contributes to Chronic Antigen Clearance Upon Immunomodulation Kumashie, Kingsley Gideon Cebula, Marcin Hagedorn, Claudia Kreppel, Florian Pils, Marina C. Koch-Nolte, Friedrich Rissiek, Björn Wirth, Dagmar Front Immunol Immunology Chronic hepatotropic viral infections are characterized by exhausted CD8+ T cells in the presence of cognate antigen in the liver. The impairment of T cell response limits the control of chronic hepatotropic viruses. Immune-modulatory strategies are attractive options to re-invigorate exhausted T cells. However, in hepatotropic viral infections, the knowledge about immune-modulatory effects on the in-situ regulation of exhausted intrahepatic CD8+ T cells is limited. In this study, we elucidated the functional heterogeneity in the pool of exhausted CD8+ T cells in the liver of mice expressing the model antigen Ova in a fraction of hepatocytes. We found a subpopulation of intrahepatic CXCR5+ Ova-specific CD8+ T cells, which are profoundly cytotoxic, exhibiting efficient metabolic functions as well as improved memory recall and self-maintenance. The intrahepatic Ova-specific CXCR5+ CD8+ T cells are possibly tissue resident cells, which may rely largely on OXPHOS and glycolysis to fuel their cellular processes. Importantly, host conditioning with CpG oligonucleotide reinvigorates and promotes exhausted T cell expansion, facilitating complete antigen eradication. The CpG oligonucleotide-mediated reinvigoration may support resident memory T cell formation and the maintenance of CXCR5+ Ova-specific CD8+ T cells in the liver. These findings suggest that CpG oligodinucleotide may preferentially target CXCR5+ CD8+ T cells for expansion to facilitate the revival of exhausted T cells. Thus, therapeutic strategies aiming to expand CXCR5+ CD8+ T cells might provide a novel approach against chronic liver infection. Frontiers Media S.A. 2021-02-03 /pmc/articles/PMC7886981/ /pubmed/33613516 http://dx.doi.org/10.3389/fimmu.2020.592328 Text en Copyright © 2021 Kumashie, Cebula, Hagedorn, Kreppel, Pils, Koch-Nolte, Rissiek and Wirth http://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
Kumashie, Kingsley Gideon
Cebula, Marcin
Hagedorn, Claudia
Kreppel, Florian
Pils, Marina C.
Koch-Nolte, Friedrich
Rissiek, Björn
Wirth, Dagmar
Improved Functionality of Exhausted Intrahepatic CXCR5+ CD8+ T Cells Contributes to Chronic Antigen Clearance Upon Immunomodulation
title Improved Functionality of Exhausted Intrahepatic CXCR5+ CD8+ T Cells Contributes to Chronic Antigen Clearance Upon Immunomodulation
title_full Improved Functionality of Exhausted Intrahepatic CXCR5+ CD8+ T Cells Contributes to Chronic Antigen Clearance Upon Immunomodulation
title_fullStr Improved Functionality of Exhausted Intrahepatic CXCR5+ CD8+ T Cells Contributes to Chronic Antigen Clearance Upon Immunomodulation
title_full_unstemmed Improved Functionality of Exhausted Intrahepatic CXCR5+ CD8+ T Cells Contributes to Chronic Antigen Clearance Upon Immunomodulation
title_short Improved Functionality of Exhausted Intrahepatic CXCR5+ CD8+ T Cells Contributes to Chronic Antigen Clearance Upon Immunomodulation
title_sort improved functionality of exhausted intrahepatic cxcr5+ cd8+ t cells contributes to chronic antigen clearance upon immunomodulation
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886981/
https://www.ncbi.nlm.nih.gov/pubmed/33613516
http://dx.doi.org/10.3389/fimmu.2020.592328
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