Functional Changes of T-Cell Subsets with Age and CMV Infection

Cytomegalovirus (CMV) latent infection and aging contribute to alterations in the function and phenotype of the T-cell pool. We have demonstrated that CMV-seropositivity is associated with the expansion of polyfunctional CD57+ T-cells in young and middle-aged individuals in response to different sti...

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Main Authors: Fakhri Hassouneh, David Goldeck, Alejandra Pera, Diana van Heemst, P. Eline Slagboom, Graham Pawelec, Rafael Solana
Format: Article
Language:English
Published: MDPI AG 2021-09-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/18/9973
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author Fakhri Hassouneh
David Goldeck
Alejandra Pera
Diana van Heemst
P. Eline Slagboom
Graham Pawelec
Rafael Solana
author_facet Fakhri Hassouneh
David Goldeck
Alejandra Pera
Diana van Heemst
P. Eline Slagboom
Graham Pawelec
Rafael Solana
author_sort Fakhri Hassouneh
collection DOAJ
description Cytomegalovirus (CMV) latent infection and aging contribute to alterations in the function and phenotype of the T-cell pool. We have demonstrated that CMV-seropositivity is associated with the expansion of polyfunctional CD57+ T-cells in young and middle-aged individuals in response to different stimuli. Here, we expand our results on the effects of age and CMV infection on T-cell functionality in a cohort of healthy middle-aged and older individuals stratified by CMV serostatus. Specifically, we studied the polyfunctional responses (degranulation, IFN-γ and TNF-α production) of CD4+, CD8+, CD8+CD56+ (NKT-like), and CD4-CD8- (DN) T-cells according to CD57 expression in response to Staphylococcal Enterotoxin B (SEB). Our results show that CD57 expression by T-cells is not only a hallmark of CMV infection in young individuals but also at older ages. CD57+ T-cells are more polyfunctional than CD57− T-cells regardless of age. CMV-seronegative individuals have no or a very low percentages of cytotoxic CD4+ T-cells (CD1017a+) and CD4+CD57+ T-cells, supporting the notion that the expansion of these T-cells only occurs in the context of CMV infection. There was a functional shift in T-cells associated with CMV seropositivity, except in the NKT-like subset. Here, we show that the effect of CMV infection and age differ among T-cell subsets and that CMV is the major driving force for the expansion of highly polyfunctional CD57+ T-cells, emphasizing the necessity of considering CMV serology in any study of immunosenescence.
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spelling doaj.art-efa038739fd04c029cfcc80743bc341c2023-11-22T13:30:34ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-012218997310.3390/ijms22189973Functional Changes of T-Cell Subsets with Age and CMV InfectionFakhri Hassouneh0David Goldeck1Alejandra Pera2Diana van Heemst3P. Eline Slagboom4Graham Pawelec5Rafael Solana6GC01—Immunology and Allergy Group, Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, SpainDepartment of Internal Medicine II, Centre for Medical Research, University of Tübingen, 72072 Tübingen, GermanyGC01—Immunology and Allergy Group, Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, SpainSection Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, 2333 Leiden, The NetherlandsMolecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, 2333 Leiden, The NetherlandsDepartment of Immunology, University of Tübingen, 72027 Tübingen, GermanyGC01—Immunology and Allergy Group, Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, SpainCytomegalovirus (CMV) latent infection and aging contribute to alterations in the function and phenotype of the T-cell pool. We have demonstrated that CMV-seropositivity is associated with the expansion of polyfunctional CD57+ T-cells in young and middle-aged individuals in response to different stimuli. Here, we expand our results on the effects of age and CMV infection on T-cell functionality in a cohort of healthy middle-aged and older individuals stratified by CMV serostatus. Specifically, we studied the polyfunctional responses (degranulation, IFN-γ and TNF-α production) of CD4+, CD8+, CD8+CD56+ (NKT-like), and CD4-CD8- (DN) T-cells according to CD57 expression in response to Staphylococcal Enterotoxin B (SEB). Our results show that CD57 expression by T-cells is not only a hallmark of CMV infection in young individuals but also at older ages. CD57+ T-cells are more polyfunctional than CD57− T-cells regardless of age. CMV-seronegative individuals have no or a very low percentages of cytotoxic CD4+ T-cells (CD1017a+) and CD4+CD57+ T-cells, supporting the notion that the expansion of these T-cells only occurs in the context of CMV infection. There was a functional shift in T-cells associated with CMV seropositivity, except in the NKT-like subset. Here, we show that the effect of CMV infection and age differ among T-cell subsets and that CMV is the major driving force for the expansion of highly polyfunctional CD57+ T-cells, emphasizing the necessity of considering CMV serology in any study of immunosenescence.https://www.mdpi.com/1422-0067/22/18/9973agingcytomegalovirusCD57T-cell response
spellingShingle Fakhri Hassouneh
David Goldeck
Alejandra Pera
Diana van Heemst
P. Eline Slagboom
Graham Pawelec
Rafael Solana
Functional Changes of T-Cell Subsets with Age and CMV Infection
International Journal of Molecular Sciences
aging
cytomegalovirus
CD57
T-cell response
title Functional Changes of T-Cell Subsets with Age and CMV Infection
title_full Functional Changes of T-Cell Subsets with Age and CMV Infection
title_fullStr Functional Changes of T-Cell Subsets with Age and CMV Infection
title_full_unstemmed Functional Changes of T-Cell Subsets with Age and CMV Infection
title_short Functional Changes of T-Cell Subsets with Age and CMV Infection
title_sort functional changes of t cell subsets with age and cmv infection
topic aging
cytomegalovirus
CD57
T-cell response
url https://www.mdpi.com/1422-0067/22/18/9973
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AT pelineslagboom functionalchangesoftcellsubsetswithageandcmvinfection
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