Ageing and latent CMV infection impact on maturation, differentiation and exhaustion profiles of T-cell receptor gammadelta T-cells

Abstract Ageing is a broad cellular process, largely affecting the immune system, especially T-lymphocytes. Additionally to immunosenescence alone, cytomegalovirus (CMV) infection is thought to have major impacts on T-cell subset composition and exhaustion. These impacts have been studied extensivel...

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Autores principales: Martine J. Kallemeijn, Anne Mieke H. Boots, Michèle Y. van der Klift, Elisabeth Brouwer, Wayel H. Abdulahad, Jan A. N. Verhaar, Jacques J. M. van Dongen, Anton W. Langerak
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:b6172dab0f5b443a97beab16c2765c3b2021-12-02T12:32:12ZAgeing and latent CMV infection impact on maturation, differentiation and exhaustion profiles of T-cell receptor gammadelta T-cells10.1038/s41598-017-05849-12045-2322https://doaj.org/article/b6172dab0f5b443a97beab16c2765c3b2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05849-1https://doaj.org/toc/2045-2322Abstract Ageing is a broad cellular process, largely affecting the immune system, especially T-lymphocytes. Additionally to immunosenescence alone, cytomegalovirus (CMV) infection is thought to have major impacts on T-cell subset composition and exhaustion. These impacts have been studied extensively in TCRαβ+ T-cells, with reduction in naive, increase in effector (memory) subsets and shifts in CD4/CD8-ratios, in conjunction with morbidity and mortality in elderly. Effects of both ageing and CMV on the TCRγδ+ T-cell compartment remain largely elusive. In the current study we investigated Vγ- and Vδ-usage, maturation, differentiation and exhaustion marker profiles of both CD4 and CD8 double-negative (DN) and CD8+TCRγδ+ T-cells in 157 individuals, age range 20–95. We observed a progressive decrease in absolute numbers of total TCRγδ+ T-cells in blood, affecting the predominant Vγ9/Vδ2 population. Aged TCRγδ+ T-cells appeared to shift from naive to more (late-stage) effector phenotypes, which appeared more prominent in case of persistent CMV infections. In addition, we found effects of both ageing and CMV on the absolute counts of exhausted TCRγδ+ T-cells. Collectively, our data show a clear impact of ageing and CMV persistence on DN and CD8+TCRγδ+ T-cells, similar to what has been reported in CD8+TCRαβ+ T-cells, indicating that they undergo similar ageing processes.Martine J. KallemeijnAnne Mieke H. BootsMichèle Y. van der KliftElisabeth BrouwerWayel H. AbdulahadJan A. N. VerhaarJacques J. M. van DongenAnton W. LangerakNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Martine J. Kallemeijn
Anne Mieke H. Boots
Michèle Y. van der Klift
Elisabeth Brouwer
Wayel H. Abdulahad
Jan A. N. Verhaar
Jacques J. M. van Dongen
Anton W. Langerak
Ageing and latent CMV infection impact on maturation, differentiation and exhaustion profiles of T-cell receptor gammadelta T-cells
description Abstract Ageing is a broad cellular process, largely affecting the immune system, especially T-lymphocytes. Additionally to immunosenescence alone, cytomegalovirus (CMV) infection is thought to have major impacts on T-cell subset composition and exhaustion. These impacts have been studied extensively in TCRαβ+ T-cells, with reduction in naive, increase in effector (memory) subsets and shifts in CD4/CD8-ratios, in conjunction with morbidity and mortality in elderly. Effects of both ageing and CMV on the TCRγδ+ T-cell compartment remain largely elusive. In the current study we investigated Vγ- and Vδ-usage, maturation, differentiation and exhaustion marker profiles of both CD4 and CD8 double-negative (DN) and CD8+TCRγδ+ T-cells in 157 individuals, age range 20–95. We observed a progressive decrease in absolute numbers of total TCRγδ+ T-cells in blood, affecting the predominant Vγ9/Vδ2 population. Aged TCRγδ+ T-cells appeared to shift from naive to more (late-stage) effector phenotypes, which appeared more prominent in case of persistent CMV infections. In addition, we found effects of both ageing and CMV on the absolute counts of exhausted TCRγδ+ T-cells. Collectively, our data show a clear impact of ageing and CMV persistence on DN and CD8+TCRγδ+ T-cells, similar to what has been reported in CD8+TCRαβ+ T-cells, indicating that they undergo similar ageing processes.
format article
author Martine J. Kallemeijn
Anne Mieke H. Boots
Michèle Y. van der Klift
Elisabeth Brouwer
Wayel H. Abdulahad
Jan A. N. Verhaar
Jacques J. M. van Dongen
Anton W. Langerak
author_facet Martine J. Kallemeijn
Anne Mieke H. Boots
Michèle Y. van der Klift
Elisabeth Brouwer
Wayel H. Abdulahad
Jan A. N. Verhaar
Jacques J. M. van Dongen
Anton W. Langerak
author_sort Martine J. Kallemeijn
title Ageing and latent CMV infection impact on maturation, differentiation and exhaustion profiles of T-cell receptor gammadelta T-cells
title_short Ageing and latent CMV infection impact on maturation, differentiation and exhaustion profiles of T-cell receptor gammadelta T-cells
title_full Ageing and latent CMV infection impact on maturation, differentiation and exhaustion profiles of T-cell receptor gammadelta T-cells
title_fullStr Ageing and latent CMV infection impact on maturation, differentiation and exhaustion profiles of T-cell receptor gammadelta T-cells
title_full_unstemmed Ageing and latent CMV infection impact on maturation, differentiation and exhaustion profiles of T-cell receptor gammadelta T-cells
title_sort ageing and latent cmv infection impact on maturation, differentiation and exhaustion profiles of t-cell receptor gammadelta t-cells
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/b6172dab0f5b443a97beab16c2765c3b
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