"This is the peer reviewed version of the following article:Riddell, N. E., Griffiths, S. J., Rivino, L., King, D. C. B., Teo, G. H., Henson, S. M., Cantisan, S., Solana, R., Kemeny, D. M., MacAry, P. A., Larbi, A. and Akbar, A. N. (2015), Multifunctional cytomegalovirus (CMV)-specific CD8+ T cells are not restricted by telomere-related senescence in young or old adults. Immunology, 144: 549–560 which has been published in final form at  doi:10.1111/imm.12409. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.This study was supported by the BBRSC (ANA, NER andSMH) and MRC (SG)

Akbar

Almanzar

Appay

Baerlocher

Berg

Betts

Blackburn

Caccamo

Cannon

Cawthon

Chidrawar

Cohen

Crompton

Dunne

Effros

Ferrando-Martinez

Fletcher

Fyhrquist

Geginat

Griffiths

Hamann

Henson

Hodes

Kapoor

Levin

Libri

Millington

Mitri

Montpetit

Nikolich-Zugich

Passos

Plunkett

Reed

Rosenberg

Rufer

Samani

Seder

Semmo

Wallace

Weng

Zhou

Immunology

PubMed

Antigen-specific multifunctional T cells that secrete interferon-γ, interleukin-2 and tumour necrosis factor-α simultaneously after activation are important for the control of many infections. It is unclear if these CD8(+) T cells are at an early or late stage of differentiation and whether telomere erosion restricts their replicative capacity. We developed a multi-parameter flow cytometric method for investigating the relationship between differentiation (CD45RA and CD27 surface phenotype), function (cytokine production) and replicative capacity (telomere length) in individual cytomegalovirus (CMV) antigen-specific CD8(+) T cells. This involves surface and intracellular cell staining coupled to fluorescence in situ hybridization to detect telomeres (flow-FISH). The end-stage/senescent CD8(+)  CD45RA(+)  CD27(-) T-cell subset increases significantly during ageing and this is exaggerated in CMV immune-responsive subjects. However, these end-stage cells do not have the shortest telomeres, implicating additional non-telomere-related mechanisms in inducing their senescence. The telomere lengths in total and CMV (NLV)-specific CD8(+) T cells in all four subsets defined by CD45RA and CD27 expression were significantly shorter in old compared with young individuals in both a Caucasian and an Asian cohort. Following stimulation by anti-CD3 or NLV peptide, similar proportions of triple-cytokine-producing cells are found in CD8(+) T cells at all stages of differentiation in both age groups. Furthermore, these multi-functional cells had intermediate telomere lengths compared with cells producing only one or two cytokines after activation. Therefore, global and CMV (NLV)-specific CD8(+) T cells that secrete interferon-γ, interleukin-2 and tumour necrosis factor-α are at an intermediate stage of differentiation and are not restricted by excessive telomere erosion

Riddell, NE

Griffiths, SJ

Rivino, L

King, DC

Teo, GH

Henson, SM

Cantisan, S

Solana, R

Kemeny, DM

MacAry, PA

Larbi, A

Akbar, AN

UCL Discovery

Multifunctional cytomegalovirus (CMV)-specific CD8(+) T cells are not restricted by telomere-related senescence in young or old adults.

Antigen-specific multifunctional T cells that secrete interferon-γ, interleukin-2 and tumour necrosis factor-α simultaneously after activation are important for the control of many infections. It is unclear if these CD8+ T cells are at an early or late stage of differentiation and whether telomere erosion restricts their replicative capacity. We developed a multi-parameter flow cytometric method for investigating the relationship between differentiation (CD45RA and CD27 surface phenotype), function (cytokine production) and replicative capacity (telomere length) in individual cytomegalovirus (CMV) antigen-specific CD8+ T cells. This involves surface and intracellular cell staining coupled to fluorescence in situ hybridization to detect telomeres (flow-FISH). The end-stage/senescent CD8+ CD45RA+ CD27− T-cell subset increases significantly during ageing and this is exaggerated in CMV immune-responsive subjects. However, these end-stage cells do not have the shortest telomeres, implicating additional non-telomere-related mechanisms in inducing their senescence. The telomere lengths in total and CMV (NLV)-specific CD8+ T cells in all four subsets defined by CD45RA and CD27 expression were significantly shorter in old compared with young individuals in both a Caucasian and an Asian cohort. Following stimulation by anti-CD3 or NLV peptide, similar proportions of triple-cytokine-producing cells are found in CD8+ T cells at all stages of differentiation in both age groups. Furthermore, these multi-functional cells had intermediate telomere lengths compared with cells producing only one or two cytokines after activation. Therefore, global and CMV (NLV)-specific CD8+ T cells that secrete interferon-γ, interleukin-2 and tumour necrosis factor-α are at an intermediate stage of differentiation and are not restricted by excessive telomere erosion

Riddell, N

Griffiths, SJ

Rivino, L

King, DCB

Teo, GH

Henson, SM

Cantisan, S

Solana, R

Kemeny, DM

MacAry, PA

Larbi, A

Akbar, AN

University of Surrey

English

Multifunctional cytomegalovirus (CMV)-specific CD8+ T cells are not restricted by telomere-related senescence in young or old adults

Riddell, N

King, DCB

Surrey Research Insight

Antigen-specific multifunctional T cells that secrete interferon-γ, interleukin-2 and tumour necrosis factor-α simultaneously after activation are important for the control of many infections. It is unclear if these CD8(+) T cells are at an early or late stage of differentiation and whether telomere erosion restricts their replicative capacity. We developed a multi-parameter flow cytometric method for investigating the relationship between differentiation (CD45RA and CD27 surface phenotype), function (cytokine production) and replicative capacity (telomere length) in individual cytomegalovirus (CMV) antigen-specific CD8(+) T cells. This involves surface and intracellular cell staining coupled to fluorescence in situ hybridization to detect telomeres (flow-FISH). The end-stage/senescent CD8(+) CD45RA(+) CD27(-) T-cell subset increases significantly during ageing and this is exaggerated in CMV immune-responsive subjects. However, these end-stage cells do not have the shortest telomeres, implicating additional non-telomere-related mechanisms in inducing their senescence. The telomere lengths in total and CMV (NLV)-specific CD8(+) T cells in all four subsets defined by CD45RA and CD27 expression were significantly shorter in old compared with young individuals in both a Caucasian and an Asian cohort. Following stimulation by anti-CD3 or NLV peptide, similar proportions of triple-cytokine-producing cells are found in CD8(+) T cells at all stages of differentiation in both age groups. Furthermore, these multi-functional cells had intermediate telomere lengths compared with cells producing only one or two cytokines after activation. Therefore, global and CMV (NLV)-specific CD8(+) T cells that secrete interferon-γ, interleukin-2 and tumour necrosis factor-α are at an intermediate stage of differentiation and are not restricted by excessive telomere erosion. </p

Riddell, Natalie E

Griffiths, Stephen J

Rivino, Laura

King, David C B

Teo, Guo H

Henson, Sian M

Cantisan, Sara

Solana, Rafael

Kemeny, David M

MacAry, Paul A

Larbi, Anis

Akbar, Arne N

Explore Bristol Research

Multifunctional cytomegalovirus (CMV)-specific CD8(+) T cells are not restricted by telomere-related senescence in young or old adults

Natalie E. Riddell

Stephen J. Griffiths

Laura Rivino

David C. B. King

Guo H. Teo

Sian M. Henson

Sara Cantisan

Rafael Solana

David M. Kemeny

Paul A. MacAry

Anis Larbi

Arne N. Akbar

Crossref

Multifunctional cytomegalovirus (CMV)-specific CD8<sup>+</sup>T cells are not restricted by telomere-related senescence in young or old adults

Queen Mary Research Online

https://qmro.qmul.ac.uk/xmlui/bitstream/handle/123456789/15829/Riddell%202014%20Multifunctional%20cytomegalovirus.pdf?sequence=1

Multifunctional cytomegalovirus (CMV)-specific CD8(+) T cells are not restricted by telomere-related senescence in young or old adults

Abstract

Similar works

Full text

Available Versions