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

Riddell, N, Griffiths, SJ, Rivino, L, King, DCB, Teo, GH, Henson, SM, Cantisan, S, Solana, R, Kemeny, DM, MacAry, PA et al, Larbi, A and Akbar, AN (2015) Multifunctional cytomegalovirus (CMV)-specific CD8+ T cells are not restricted by telomere-related senescence in young or old adults Immunology, 144 (4). pp. 549-560.

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Abstract

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.

Item Type:	Article
Subjects :	Biosciences
Divisions :	Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :	Name Email ORCID Riddell, N Griffiths, SJ Rivino, L King, DCB Teo, GH Henson, SM Cantisan, S Solana, R Kemeny, DM MacAry, PA Larbi, A Akbar, AN
Date :	April 2015
Identification Number :	10.1111/imm.12409
Copyright Disclaimer :	© 2014 The Authors. Immunology published by John Wiley & Sons Ltd. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ or send a letter to Creative Commons, PO Box 1866, Mountain View, CA 94042, USA.
Uncontrolled Keywords :	CD8+ T cells, Cytomegalovirus, Multi-functional, Senescence, Telomere
Depositing User :	Symplectic Elements
Date Deposited :	13 Mar 2017 12:01
Last Modified :	31 Oct 2017 19:11
URI:	http://epubs.surrey.ac.uk/id/eprint/813758

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