Aging and cytomegalovirus infection differentially and jointly affect distinct circulating T cell subsets in humans

Anne M Wertheimer, Michael S. Bennett, Byung Park, Jennifer L. Uhrlaub, Carmine Martinez, Vesna Pulko, Noreen L. Currier, Dragana Nikolich-Zugich, Jeffrey Kaye, Janko Nikolich-Zugich

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

The impact of intrinsic aging upon human peripheral blood T cell subsets remains incompletely quantified and understood. This impact must be distinguished from the influence of latent persistent microorganisms, particularly CMV, which has been associated with age-related changes in the T cell pool. In a cross-sectional cohort of 152 CMV-negative individuals, aged 21-101 y, we found that aging correlated strictly to an absolute loss of naive CD8, but not CD4, T cells but, contrary to many reports, did not lead to an increase in memory T cell numbers. The loss of naive CD8 T cells was not altered by CMV in 239 subjects (range 21-96 y), but the decline in CD4+ naive cells showed significance in CMV+ individuals. These individuals also exhibited an absolute increase in the effector/effector memory CD4+ and CD8+ cells with age. That increase was seen mainly, if not exclusively, in older subjects with elevated anti-CMVAb titers, suggesting that efficacy of viral control over time may determine the magnitude of CMV impact upon T cell memory, and perhaps upon immune defense. These findings provide important new insights into the age-related changes in the peripheral blood pool of older adults, demonstrating that aging and CMV exert both distinct and joint influence upon blood T cell homeostasis in humans.

Original languageEnglish (US)
Pages (from-to)2143-2155
Number of pages13
JournalJournal of Immunology
Volume192
Issue number5
DOIs
StatePublished - Mar 1 2014

Fingerprint

Cytomegalovirus Infections
T-Lymphocyte Subsets
T-Lymphocytes
Blood Cells
Homeostasis
Cell Count
Joints

ASJC Scopus subject areas

  • Immunology

Cite this

Aging and cytomegalovirus infection differentially and jointly affect distinct circulating T cell subsets in humans. / Wertheimer, Anne M; Bennett, Michael S.; Park, Byung; Uhrlaub, Jennifer L.; Martinez, Carmine; Pulko, Vesna; Currier, Noreen L.; Nikolich-Zugich, Dragana; Kaye, Jeffrey; Nikolich-Zugich, Janko.

In: Journal of Immunology, Vol. 192, No. 5, 01.03.2014, p. 2143-2155.

Research output: Contribution to journalArticle

Wertheimer, AM, Bennett, MS, Park, B, Uhrlaub, JL, Martinez, C, Pulko, V, Currier, NL, Nikolich-Zugich, D, Kaye, J & Nikolich-Zugich, J 2014, 'Aging and cytomegalovirus infection differentially and jointly affect distinct circulating T cell subsets in humans', Journal of Immunology, vol. 192, no. 5, pp. 2143-2155. https://doi.org/10.4049/jimmunol.1301721
Wertheimer, Anne M ; Bennett, Michael S. ; Park, Byung ; Uhrlaub, Jennifer L. ; Martinez, Carmine ; Pulko, Vesna ; Currier, Noreen L. ; Nikolich-Zugich, Dragana ; Kaye, Jeffrey ; Nikolich-Zugich, Janko. / Aging and cytomegalovirus infection differentially and jointly affect distinct circulating T cell subsets in humans. In: Journal of Immunology. 2014 ; Vol. 192, No. 5. pp. 2143-2155.
@article{631b93856de3483e91526fda75770ae3,
title = "Aging and cytomegalovirus infection differentially and jointly affect distinct circulating T cell subsets in humans",
abstract = "The impact of intrinsic aging upon human peripheral blood T cell subsets remains incompletely quantified and understood. This impact must be distinguished from the influence of latent persistent microorganisms, particularly CMV, which has been associated with age-related changes in the T cell pool. In a cross-sectional cohort of 152 CMV-negative individuals, aged 21-101 y, we found that aging correlated strictly to an absolute loss of naive CD8, but not CD4, T cells but, contrary to many reports, did not lead to an increase in memory T cell numbers. The loss of naive CD8 T cells was not altered by CMV in 239 subjects (range 21-96 y), but the decline in CD4+ naive cells showed significance in CMV+ individuals. These individuals also exhibited an absolute increase in the effector/effector memory CD4+ and CD8+ cells with age. That increase was seen mainly, if not exclusively, in older subjects with elevated anti-CMVAb titers, suggesting that efficacy of viral control over time may determine the magnitude of CMV impact upon T cell memory, and perhaps upon immune defense. These findings provide important new insights into the age-related changes in the peripheral blood pool of older adults, demonstrating that aging and CMV exert both distinct and joint influence upon blood T cell homeostasis in humans.",
author = "Wertheimer, {Anne M} and Bennett, {Michael S.} and Byung Park and Uhrlaub, {Jennifer L.} and Carmine Martinez and Vesna Pulko and Currier, {Noreen L.} and Dragana Nikolich-Zugich and Jeffrey Kaye and Janko Nikolich-Zugich",
year = "2014",
month = "3",
day = "1",
doi = "10.4049/jimmunol.1301721",
language = "English (US)",
volume = "192",
pages = "2143--2155",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "5",

}

TY - JOUR

T1 - Aging and cytomegalovirus infection differentially and jointly affect distinct circulating T cell subsets in humans

AU - Wertheimer, Anne M

AU - Bennett, Michael S.

AU - Park, Byung

AU - Uhrlaub, Jennifer L.

AU - Martinez, Carmine

AU - Pulko, Vesna

AU - Currier, Noreen L.

AU - Nikolich-Zugich, Dragana

AU - Kaye, Jeffrey

AU - Nikolich-Zugich, Janko

PY - 2014/3/1

Y1 - 2014/3/1

N2 - The impact of intrinsic aging upon human peripheral blood T cell subsets remains incompletely quantified and understood. This impact must be distinguished from the influence of latent persistent microorganisms, particularly CMV, which has been associated with age-related changes in the T cell pool. In a cross-sectional cohort of 152 CMV-negative individuals, aged 21-101 y, we found that aging correlated strictly to an absolute loss of naive CD8, but not CD4, T cells but, contrary to many reports, did not lead to an increase in memory T cell numbers. The loss of naive CD8 T cells was not altered by CMV in 239 subjects (range 21-96 y), but the decline in CD4+ naive cells showed significance in CMV+ individuals. These individuals also exhibited an absolute increase in the effector/effector memory CD4+ and CD8+ cells with age. That increase was seen mainly, if not exclusively, in older subjects with elevated anti-CMVAb titers, suggesting that efficacy of viral control over time may determine the magnitude of CMV impact upon T cell memory, and perhaps upon immune defense. These findings provide important new insights into the age-related changes in the peripheral blood pool of older adults, demonstrating that aging and CMV exert both distinct and joint influence upon blood T cell homeostasis in humans.

AB - The impact of intrinsic aging upon human peripheral blood T cell subsets remains incompletely quantified and understood. This impact must be distinguished from the influence of latent persistent microorganisms, particularly CMV, which has been associated with age-related changes in the T cell pool. In a cross-sectional cohort of 152 CMV-negative individuals, aged 21-101 y, we found that aging correlated strictly to an absolute loss of naive CD8, but not CD4, T cells but, contrary to many reports, did not lead to an increase in memory T cell numbers. The loss of naive CD8 T cells was not altered by CMV in 239 subjects (range 21-96 y), but the decline in CD4+ naive cells showed significance in CMV+ individuals. These individuals also exhibited an absolute increase in the effector/effector memory CD4+ and CD8+ cells with age. That increase was seen mainly, if not exclusively, in older subjects with elevated anti-CMVAb titers, suggesting that efficacy of viral control over time may determine the magnitude of CMV impact upon T cell memory, and perhaps upon immune defense. These findings provide important new insights into the age-related changes in the peripheral blood pool of older adults, demonstrating that aging and CMV exert both distinct and joint influence upon blood T cell homeostasis in humans.

UR - http://www.scopus.com/inward/record.url?scp=84896501298&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84896501298&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1301721

DO - 10.4049/jimmunol.1301721

M3 - Article

C2 - 24501199

AN - SCOPUS:84896501298

VL - 192

SP - 2143

EP - 2155

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 5

ER -