Lower proportion of naïve peripheral CD8+ T cells and an unopposed pro-inflammatory response to human Cytomegalovirus proteins in vitro are associated with longer survival in very elderly people

Derhovanessian, Evelyna; Maier, Andrea B.; Hähnel, Karin; Zelba, Henning; de Craen, Anton J. M.; Roelofs, Helene; Slagboom, Eline P.; Westendorp, Rudi G. J.; Pawelec, Graham

doi:10.1007/s11357-012-9425-7

Cited by 102T-cell and B-cell ImmunologyCytomegalovirus and herpesvirus researchImmune responses and vaccinations

Lower proportion of naïve peripheral CD8+ T cells and an unopposed pro-inflammatory response to human Cytomegalovirus proteins in vitro are associated with longer survival in very elderly people

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Derhovanessian, Evelyna, Maier, Andrea B., Hähnel, Karin, Zelba, Henning, de Craen, Anton J. M., Roelofs, Helene, Slagboom, Eline P., Westendorp, Rudi G. J. +1 more·2013·AGE

DOI 10.1007/s11357-012-9425-7PMC PMC3705124

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Abstract

The low percentages of naïve T cells commonly observed in elderly people are thought to be causally associated with mortality, primarily from infectious disease, and are taken as a hallmark of "immunosenescence". Whether low levels of naive cells actually do associate with mortality has, however, not been tested in longitudinal studies. Here, we present correlations between peripheral T-cell phenotypes and 8-year survival in individuals from the population-based prospective Leiden 85-plus Study. Counter-intuitively, we found that a lower frequency of naïve CD8+ T cells (characterized as CD45RA+CCR7+CD27+CD28+) at baseline (>88 years) correlated with significantly better survival, while there was a tendency for the reciprocal accumulation of late-differentiated effector memory cells (CD45RA-CCR7-CD27-CD28-) also to associate with better survival. These findings suggest that better retention of memory cells specific for previously encountered antigens may provide a survival advantage in this particular population. Given the prevalence of Cytomegalovirus (CMV) and its reported association with immunosenescence, we tested whether memory for this potential pathogen was relevant to survival. We found that individuals mounting an exclusively pro-inflammatory ex vivo response (TNF, IFN-γ, IL-17) to the major CMV target molecules pp65 and IE1 had a significant survival advantage over those also having anti-inflammatory responses (IL-10). These findings suggest that higher levels of naïve T cells may not necessarily be associated with a survival advantage and imply that the nature of immunosurveillance against CMV may be crucial for remaining longevity, at least in the very elderly.

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A lower proportion of naïve CD8+ T cells, a higher proportion of memory CD8+ T cells, and a robust pro-inflammatory response to CMV, are associated with better survival in a longitudinal analysis of elderly individuals.
“For example, it has been shown that a lower proportion of naïve CD8+ T cells, a higher proportion of memory CD8+ T cells, and a robust pro-inflammatory response to CMV, are associated with better survival in a longitudinal analysis of elderly individuals (Derhovanessian et al. 2013).”
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Phenotypic and functional immune attributes predicting survival in very elderly people (47.7)
Pawelec, G., Maier, A. B., Hähnel, K., Zelba, H., de Craen, A. J. M., Roelofs, H., Slagboom, P. E., Westendorp, R. G. J., & Derhovanessian, E. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.188.supp.47.7
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Authors: Derhovanessian, E., Maier, A. B., Hähnel, K., Zelba, H., de Craen, A. J. M., Roelofs, H., Slagboom, E. P., Westendorp, R. G. J., & Pawelec, G.
Affiliations: University of Tübingen (DE)
Leiden University Medical Center (NL)
Leiden University (NL)
Corresponding author: Derhovanessian, Evelyna
ORCID: Maier, Andrea B.
Zelba, Henning
Roelofs, Helene
Westendorp, Rudi G. J.
Pawelec, Graham
Venue: AGE
Publisher: Springer Science and Business Media LLC
Published: 2012-06-04
Volume: 35
Issue: 4
Pages: 1387-1399
ISSN: 0161-9152 (ISSN-L)
1574-4647
DOI: 10.1007/s11357-012-9425-7
PMC: PMC3705124
OpenAlex: W2117975451
Cited by: 102
References: 48
Citations by year: 2026: 1 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 5 · 2021: 8 · 2020: 8 · 2019: 7 · 2018: 6 · 2017: 11 · 2016: 12 · 2015: 11 · 2014: 11 · 2013: 8 · 2012: 3
FWCI: 4.62
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/2.0 (tdm)
Locations: AGE (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
VU Research Portal (publishedVersion, other-oa)
Data Archiving and Networked Services (DANS) (submittedVersion)
Leiden Repository (Leiden University) (submittedVersion)
Minerva Access (University of Melbourne) (submittedVersion, cc-by)
Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders: Eli Lilly and Company
European Commission (FP6 036894, FP7259679, 259679)
Deutsche Forschungsgemeinschaft (PA 361/14-1, DFG PA 361/14-1, /14-1)
Universiteit Leiden (050-060-810, 05040202)
ZonMw (05040202, 050-060-810)
Bundesministerium für Bildung und Forschung (0315890F)
Albert-Ludwigs-Universität Freiburg
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (050.060.810, 05040202)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords: immunosenescence, naive CD8+ T cells, oldest old, survival, cytomegalovirus, pp65, IE1, IL-10, memory T cells, CD45RA, CCR7, CD27, CD28, longevity, immune surveillance, Leiden 85-plus Study
MeSH terms: Aged, 80 and over, Aging, Antigens, Viral, Cytomegalovirus, Female, Flow Cytometry, Follow-Up Studies, Humans, Immunity, Cellular, Longevity, Male, Netherlands, Population Surveillance, Prospective Studies, Viral Proteins, Survival Rate, CD8-Positive T-Lymphocytes

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Lower proportion of naïve peripheral CD8+ T cells and an unopposed pro-inflammatory response to human Cytomegalovirus proteins in vitro are associated with longer survival in very elderly people

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