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...
Main Authors: | , , , , , , |
---|---|
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 |
_version_ | 1797518931451183104 |
---|---|
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. |
first_indexed | 2024-03-10T07:36:17Z |
format | Article |
id | doaj.art-efa038739fd04c029cfcc80743bc341c |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-10T07:36:17Z |
publishDate | 2021-09-01 |
publisher | MDPI AG |
record_format | Article |
series | International Journal of Molecular Sciences |
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 |
work_keys_str_mv | AT fakhrihassouneh functionalchangesoftcellsubsetswithageandcmvinfection AT davidgoldeck functionalchangesoftcellsubsetswithageandcmvinfection AT alejandrapera functionalchangesoftcellsubsetswithageandcmvinfection AT dianavanheemst functionalchangesoftcellsubsetswithageandcmvinfection AT pelineslagboom functionalchangesoftcellsubsetswithageandcmvinfection AT grahampawelec functionalchangesoftcellsubsetswithageandcmvinfection AT rafaelsolana functionalchangesoftcellsubsetswithageandcmvinfection |