Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
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
_version_ 1783665570240004096
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
work_keys_str_mv AT parryhelenm pd1isimprintedoncytomegalovirusspecificcd4tcellsandattenuatesth1cytokineproductionwhilstmaintainingcytotoxicity
AT dowellalexanderc pd1isimprintedoncytomegalovirusspecificcd4tcellsandattenuatesth1cytokineproductionwhilstmaintainingcytotoxicity
AT zuojianmin pd1isimprintedoncytomegalovirusspecificcd4tcellsandattenuatesth1cytokineproductionwhilstmaintainingcytotoxicity
AT vermakriti pd1isimprintedoncytomegalovirusspecificcd4tcellsandattenuatesth1cytokineproductionwhilstmaintainingcytotoxicity
AT kinsellafrancescaam pd1isimprintedoncytomegalovirusspecificcd4tcellsandattenuatesth1cytokineproductionwhilstmaintainingcytotoxicity
AT begumjusnara pd1isimprintedoncytomegalovirusspecificcd4tcellsandattenuatesth1cytokineproductionwhilstmaintainingcytotoxicity
AT croftwayne pd1isimprintedoncytomegalovirusspecificcd4tcellsandattenuatesth1cytokineproductionwhilstmaintainingcytotoxicity
AT sharmaoatesarchana pd1isimprintedoncytomegalovirusspecificcd4tcellsandattenuatesth1cytokineproductionwhilstmaintainingcytotoxicity
AT prattguy pd1isimprintedoncytomegalovirusspecificcd4tcellsandattenuatesth1cytokineproductionwhilstmaintainingcytotoxicity
AT mosspaul pd1isimprintedoncytomegalovirusspecificcd4tcellsandattenuatesth1cytokineproductionwhilstmaintainingcytotoxicity