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PD-1 is imprinted on cytomegalovirus-specific CD4+ T cells and attenuates Th1 cytokine production whilst maintaining cytotoxicity
PD-1 is expressed on exhausted T cells in cancer patients but its physiological role remains uncertain. We determined the phenotype, function and transcriptional correlates of PD-1 expression on cytomegalovirus-specific CD4+ T cells during latent infection. PD-1 expression ranged from 10–85% and rem...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963093/ https://www.ncbi.nlm.nih.gov/pubmed/33662046 http://dx.doi.org/10.1371/journal.ppat.1009349 |
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author | Parry, Helen M. Dowell, Alexander C. Zuo, Jianmin Verma, Kriti Kinsella, Francesca A. M. Begum, Jusnara Croft, Wayne Sharma-Oates, Archana Pratt, Guy Moss, Paul |
author_facet | Parry, Helen M. Dowell, Alexander C. Zuo, Jianmin Verma, Kriti Kinsella, Francesca A. M. Begum, Jusnara Croft, Wayne Sharma-Oates, Archana Pratt, Guy Moss, Paul |
author_sort | Parry, Helen M. |
collection | PubMed |
description | PD-1 is expressed on exhausted T cells in cancer patients but its physiological role remains uncertain. We determined the phenotype, function and transcriptional correlates of PD-1 expression on cytomegalovirus-specific CD4+ T cells during latent infection. PD-1 expression ranged from 10–85% and remained stable over time within individual donors. This ‘setpoint’ was correlated with viral load at primary infection. PD-1+ CD4+ T cells display strong cytotoxic function but generate low levels of Th1 cytokines which is only partially reversed by PD-1 blockade. TCR clonotypes showed variable sharing between PD-1+ and PD-1- CMV-specific cells indicating that PD-1 status is defined either during T cell priming or subsequent clonal expansion. Physiological PD-1+ CD4+ T cells therefore display a unique ‘high cytotoxicity-low cytokine’ phenotype and may act to suppress viral reactivation whilst minimizing tissue inflammation. Improved understanding of the physiological role of PD-1 will help to delineate the mechanisms, and potential reversal, of PD-1+ CD4+ T cell exhaustion in patients with malignant disease. |
format | Online Article Text |
id | pubmed-7963093 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-79630932021-03-26 PD-1 is imprinted on cytomegalovirus-specific CD4+ T cells and attenuates Th1 cytokine production whilst maintaining cytotoxicity Parry, Helen M. Dowell, Alexander C. Zuo, Jianmin Verma, Kriti Kinsella, Francesca A. M. Begum, Jusnara Croft, Wayne Sharma-Oates, Archana Pratt, Guy Moss, Paul PLoS Pathog Research Article PD-1 is expressed on exhausted T cells in cancer patients but its physiological role remains uncertain. We determined the phenotype, function and transcriptional correlates of PD-1 expression on cytomegalovirus-specific CD4+ T cells during latent infection. PD-1 expression ranged from 10–85% and remained stable over time within individual donors. This ‘setpoint’ was correlated with viral load at primary infection. PD-1+ CD4+ T cells display strong cytotoxic function but generate low levels of Th1 cytokines which is only partially reversed by PD-1 blockade. TCR clonotypes showed variable sharing between PD-1+ and PD-1- CMV-specific cells indicating that PD-1 status is defined either during T cell priming or subsequent clonal expansion. Physiological PD-1+ CD4+ T cells therefore display a unique ‘high cytotoxicity-low cytokine’ phenotype and may act to suppress viral reactivation whilst minimizing tissue inflammation. Improved understanding of the physiological role of PD-1 will help to delineate the mechanisms, and potential reversal, of PD-1+ CD4+ T cell exhaustion in patients with malignant disease. Public Library of Science 2021-03-04 /pmc/articles/PMC7963093/ /pubmed/33662046 http://dx.doi.org/10.1371/journal.ppat.1009349 Text en © 2021 Parry 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Parry, Helen M. Dowell, Alexander C. Zuo, Jianmin Verma, Kriti Kinsella, Francesca A. M. Begum, Jusnara Croft, Wayne Sharma-Oates, Archana Pratt, Guy Moss, Paul PD-1 is imprinted on cytomegalovirus-specific CD4+ T cells and attenuates Th1 cytokine production whilst maintaining cytotoxicity |
title | PD-1 is imprinted on cytomegalovirus-specific CD4+ T cells and attenuates Th1 cytokine production whilst maintaining cytotoxicity |
title_full | PD-1 is imprinted on cytomegalovirus-specific CD4+ T cells and attenuates Th1 cytokine production whilst maintaining cytotoxicity |
title_fullStr | PD-1 is imprinted on cytomegalovirus-specific CD4+ T cells and attenuates Th1 cytokine production whilst maintaining cytotoxicity |
title_full_unstemmed | PD-1 is imprinted on cytomegalovirus-specific CD4+ T cells and attenuates Th1 cytokine production whilst maintaining cytotoxicity |
title_short | PD-1 is imprinted on cytomegalovirus-specific CD4+ T cells and attenuates Th1 cytokine production whilst maintaining cytotoxicity |
title_sort | pd-1 is imprinted on cytomegalovirus-specific cd4+ t cells and attenuates th1 cytokine production whilst maintaining cytotoxicity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963093/ https://www.ncbi.nlm.nih.gov/pubmed/33662046 http://dx.doi.org/10.1371/journal.ppat.1009349 |
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