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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-03-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009349&type=printable |
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| author | Helen M Parry Alexander C Dowell Jianmin Zuo Kriti Verma Francesca A M Kinsella Jusnara Begum Wayne Croft Archana Sharma-Oates Guy Pratt Paul Moss |
| author_facet | Helen M Parry Alexander C Dowell Jianmin Zuo Kriti Verma Francesca A M Kinsella Jusnara Begum Wayne Croft Archana Sharma-Oates Guy Pratt Paul Moss |
| author_sort | Helen M Parry |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-24af3b309b9e44e4abf6cd1d20def486 |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2021-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-24af3b309b9e44e4abf6cd1d20def4862025-08-20T02:33:18ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742021-03-01173e100934910.1371/journal.ppat.1009349PD-1 is imprinted on cytomegalovirus-specific CD4+ T cells and attenuates Th1 cytokine production whilst maintaining cytotoxicity.Helen M ParryAlexander C DowellJianmin ZuoKriti VermaFrancesca A M KinsellaJusnara BegumWayne CroftArchana Sharma-OatesGuy PrattPaul MossPD-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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009349&type=printable |
| spellingShingle | Helen M Parry Alexander C Dowell Jianmin Zuo Kriti Verma Francesca A M Kinsella Jusnara Begum Wayne Croft Archana Sharma-Oates Guy Pratt Paul Moss PD-1 is imprinted on cytomegalovirus-specific CD4+ T cells and attenuates Th1 cytokine production whilst maintaining cytotoxicity. PLoS Pathogens |
| 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 |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009349&type=printable |
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