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

The DOI matches its Crossref record; 47 of the 48 references it cites were found in a registry or an index.

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

Open access
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·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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Crossref · 10.1007/s11357-012-9425-7

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Figures

Fig. 1 CMV seropositivity and distribution of T-cell phenotypes. Frequency of naïve and late-differentiated memory T cells within CD8+ (a) and CD4+ T cells (b) in seven CMV-seronegative (CMV−) and 41 CMV-seropositive (CMV+) individuals. Frequency of T cells carrying putative senescence markers CD57+ (c) and KLRG-1 (d) on CD4+ and CD8+ T cells were compared in the same individuals. Horizontal bars represent the median of each group
Fig. 1 CMV seropositivity and distribution of T-cell phenotypes. Frequency of naïve and late-differentiated memory T cells within CD8+ (a) and CD4+ T cells (b) in seven CMV-seronegative (CMV−) and 41 CMV-seropositive (CMV+) individuals. Frequency of T cells carrying putative senescence markers CD57+ (c) and KLRG-1 (d) on CD4+ and CD8+ T cells were compared in the same individuals. Horizontal bars represent the median of each groupCC BY · PubMed Central
Fig. 2 FACS plots demonstrating production of INFγ (upper row), TNF (middle row), and IL-10 (lower row) in the CD3+ gated population. The unstimulated control (shown in the left-hand panel) was used to set the cut-off for cytokine production
Fig. 2 FACS plots demonstrating production of INFγ (upper row), TNF (middle row), and IL-10 (lower row) in the CD3+ gated population. The unstimulated control (shown in the left-hand panel) was used to set the cut-off for cytokine productionCC BY · PubMed Central
Fig. 3 Correlation analysis between the in vitro immune response against immunodominant CMV antigens and mortality in individuals 88 years old at baseline. Kaplan–Meier survival curves for 21 CMV-seropositive individuals according to response to either pp65 or IE1 (a), or pp65 or IE1 (b) are shown. Donors were grouped according to the type of cytokine response; only pro-inflammatory—IFNγ, TNF, and/or IL-17 in the absence of any IL-10 production (black line), pro-/anti-inflammatory—IL-10 production by CD4+ and/or CD8+ T cells together or in the absence of pro-inflammatory cytokines (gray line)
Fig. 3 Correlation analysis between the in vitro immune response against immunodominant CMV antigens and mortality in individuals 88 years old at baseline. Kaplan–Meier survival curves for 21 CMV-seropositive individuals according to response to either pp65 or IE1 (a), or pp65 or IE1 (b) are shown. Donors were grouped according to the type of cytokine response; only pro-inflammatory—IFNγ, TNF, and/or IL-17 in the absence of any IL-10 production (black line), pro-/anti-inflammatory—IL-10 production by CD4+ and/or CD8+ T cells together or in the absence of pro-inflammatory cytokines (gray line)CC BY · PubMed Central

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Research works printed but not linked: 1

  1. Murasko DM, Weiner P, Kaye D (1988) Association of lack of mitogen-induced lymphocyte proliferation with increased mortality in the elderly. Aging Immunol Infect Dis 1:1–6

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Metadata

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
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
Licence
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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