Relationship between cytomegalovirus (CMV) IgG serology, detectable CMV DNA in peripheral monocytes, and CMV pp65 495-503-specific CD8 + T cells in older adults

Sean Leng, Tao Qu, Richard David Semba, Huifen Li, Xu Yao, Tricia Nilles, Xi Yang, Bhavish Manwani, Jeremy D Walston, Luigi Ferrucci, Linda P Fried, Joseph Bernard Margolick, Jay Bream

Research output: Contribution to journalArticle

Abstract

In immunocompetent individuals, cytomegalovirus (CMV) is thought to persist in a latent state in monocytes and myeloid progenitor cells, establishing a lifelong infection. In CMV-seropositive older adults, aging has been associated with both expansion of CMV pp65 495-503-specific CD8 + T cell clones and shrinkage of the T cell repertoire that characterize T cell immunosenescence. In fact it has been suggested that chronic CMV infection is a driving force in age-related T cell immunosenescence. In older adults, chronic CMV infection is conventionally diagnosed by positive IgG serology which does not distinguish between past and persistent infections. To better define the relationship between chronic CMV infection and expansion of CMV pp65 495-503-specific CD8 + T cells, we directly assessed CMV viral DNA in monocyte-enriched peripheral blood mononuclear cells in 16 HLA-A2-positive elderly volunteers (mean age = 83 years). While all participants had positive CMV IgG serology by enzyme-linked immunosorbent assays, only nine (56%) had detectable CMV DNA by nested polymerase chain reaction. These nine individuals had significantly higher percentages of CMV pp65 495-503 tetramer-positive CD8 + T cells (median = 1.3%) than those without detectable CMV DNA (median = 0.1%; p <0.001). Absolute CMV IgG antibody titers did not differ between these two groups (median = 54.6 vs 44.2 EU/ml, respectively, p = 0.4). CMV IgM titers were negative for all 16 participants, suggesting that recent primary CMV infection was unlikely. These results demonstrate a strong association between the presence of CMV DNA in peripheral monocytes and the expansion of CD8 + T cells specific for the CMV immunodominant epitope pp65 495-503. Although the sample size in this study is relatively small, these findings provide initial evidence suggesting the heterogeneity of CMV IgG-seropositive older adult population and CMV viral DNA detection in peripheral monocytes as an informative tool to better understand the relationship between chronic CMV infection and T cell immunosenescence.

Original languageEnglish (US)
Pages (from-to)607-614
Number of pages8
JournalAge
Volume33
Issue number4
DOIs
StatePublished - Dec 2011

Fingerprint

Serology
Cytomegalovirus
Monocytes
Immunoglobulin G
T-Lymphocytes
DNA
Cytomegalovirus Infections
Viral DNA
Myeloid Progenitor Cells
HLA-A2 Antigen
Immunodominant Epitopes
DNA-Directed DNA Polymerase
Infection
Sample Size
Immunoglobulin M
Volunteers
Blood Cells

Keywords

  • CMV IgG serology
  • CMV pp65 -specific CD8 T cells
  • Monocytic CMV DNA
  • Older adults

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

Cite this

@article{06bfbd748d23461088c2e2bfc8b727ed,
title = "Relationship between cytomegalovirus (CMV) IgG serology, detectable CMV DNA in peripheral monocytes, and CMV pp65 495-503-specific CD8 + T cells in older adults",
abstract = "In immunocompetent individuals, cytomegalovirus (CMV) is thought to persist in a latent state in monocytes and myeloid progenitor cells, establishing a lifelong infection. In CMV-seropositive older adults, aging has been associated with both expansion of CMV pp65 495-503-specific CD8 + T cell clones and shrinkage of the T cell repertoire that characterize T cell immunosenescence. In fact it has been suggested that chronic CMV infection is a driving force in age-related T cell immunosenescence. In older adults, chronic CMV infection is conventionally diagnosed by positive IgG serology which does not distinguish between past and persistent infections. To better define the relationship between chronic CMV infection and expansion of CMV pp65 495-503-specific CD8 + T cells, we directly assessed CMV viral DNA in monocyte-enriched peripheral blood mononuclear cells in 16 HLA-A2-positive elderly volunteers (mean age = 83 years). While all participants had positive CMV IgG serology by enzyme-linked immunosorbent assays, only nine (56{\%}) had detectable CMV DNA by nested polymerase chain reaction. These nine individuals had significantly higher percentages of CMV pp65 495-503 tetramer-positive CD8 + T cells (median = 1.3{\%}) than those without detectable CMV DNA (median = 0.1{\%}; p <0.001). Absolute CMV IgG antibody titers did not differ between these two groups (median = 54.6 vs 44.2 EU/ml, respectively, p = 0.4). CMV IgM titers were negative for all 16 participants, suggesting that recent primary CMV infection was unlikely. These results demonstrate a strong association between the presence of CMV DNA in peripheral monocytes and the expansion of CD8 + T cells specific for the CMV immunodominant epitope pp65 495-503. Although the sample size in this study is relatively small, these findings provide initial evidence suggesting the heterogeneity of CMV IgG-seropositive older adult population and CMV viral DNA detection in peripheral monocytes as an informative tool to better understand the relationship between chronic CMV infection and T cell immunosenescence.",
keywords = "CMV IgG serology, CMV pp65 -specific CD8 T cells, Monocytic CMV DNA, Older adults",
author = "Sean Leng and Tao Qu and Semba, {Richard David} and Huifen Li and Xu Yao and Tricia Nilles and Xi Yang and Bhavish Manwani and Walston, {Jeremy D} and Luigi Ferrucci and Fried, {Linda P} and Margolick, {Joseph Bernard} and Jay Bream",
year = "2011",
month = "12",
doi = "10.1007/s11357-011-9205-9",
language = "English (US)",
volume = "33",
pages = "607--614",
journal = "GeroScience",
issn = "2509-2715",
publisher = "Springer International Publishing AG",
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TY - JOUR

T1 - Relationship between cytomegalovirus (CMV) IgG serology, detectable CMV DNA in peripheral monocytes, and CMV pp65 495-503-specific CD8 + T cells in older adults

AU - Leng, Sean

AU - Qu, Tao

AU - Semba, Richard David

AU - Li, Huifen

AU - Yao, Xu

AU - Nilles, Tricia

AU - Yang, Xi

AU - Manwani, Bhavish

AU - Walston, Jeremy D

AU - Ferrucci, Luigi

AU - Fried, Linda P

AU - Margolick, Joseph Bernard

AU - Bream, Jay

PY - 2011/12

Y1 - 2011/12

N2 - In immunocompetent individuals, cytomegalovirus (CMV) is thought to persist in a latent state in monocytes and myeloid progenitor cells, establishing a lifelong infection. In CMV-seropositive older adults, aging has been associated with both expansion of CMV pp65 495-503-specific CD8 + T cell clones and shrinkage of the T cell repertoire that characterize T cell immunosenescence. In fact it has been suggested that chronic CMV infection is a driving force in age-related T cell immunosenescence. In older adults, chronic CMV infection is conventionally diagnosed by positive IgG serology which does not distinguish between past and persistent infections. To better define the relationship between chronic CMV infection and expansion of CMV pp65 495-503-specific CD8 + T cells, we directly assessed CMV viral DNA in monocyte-enriched peripheral blood mononuclear cells in 16 HLA-A2-positive elderly volunteers (mean age = 83 years). While all participants had positive CMV IgG serology by enzyme-linked immunosorbent assays, only nine (56%) had detectable CMV DNA by nested polymerase chain reaction. These nine individuals had significantly higher percentages of CMV pp65 495-503 tetramer-positive CD8 + T cells (median = 1.3%) than those without detectable CMV DNA (median = 0.1%; p <0.001). Absolute CMV IgG antibody titers did not differ between these two groups (median = 54.6 vs 44.2 EU/ml, respectively, p = 0.4). CMV IgM titers were negative for all 16 participants, suggesting that recent primary CMV infection was unlikely. These results demonstrate a strong association between the presence of CMV DNA in peripheral monocytes and the expansion of CD8 + T cells specific for the CMV immunodominant epitope pp65 495-503. Although the sample size in this study is relatively small, these findings provide initial evidence suggesting the heterogeneity of CMV IgG-seropositive older adult population and CMV viral DNA detection in peripheral monocytes as an informative tool to better understand the relationship between chronic CMV infection and T cell immunosenescence.

AB - In immunocompetent individuals, cytomegalovirus (CMV) is thought to persist in a latent state in monocytes and myeloid progenitor cells, establishing a lifelong infection. In CMV-seropositive older adults, aging has been associated with both expansion of CMV pp65 495-503-specific CD8 + T cell clones and shrinkage of the T cell repertoire that characterize T cell immunosenescence. In fact it has been suggested that chronic CMV infection is a driving force in age-related T cell immunosenescence. In older adults, chronic CMV infection is conventionally diagnosed by positive IgG serology which does not distinguish between past and persistent infections. To better define the relationship between chronic CMV infection and expansion of CMV pp65 495-503-specific CD8 + T cells, we directly assessed CMV viral DNA in monocyte-enriched peripheral blood mononuclear cells in 16 HLA-A2-positive elderly volunteers (mean age = 83 years). While all participants had positive CMV IgG serology by enzyme-linked immunosorbent assays, only nine (56%) had detectable CMV DNA by nested polymerase chain reaction. These nine individuals had significantly higher percentages of CMV pp65 495-503 tetramer-positive CD8 + T cells (median = 1.3%) than those without detectable CMV DNA (median = 0.1%; p <0.001). Absolute CMV IgG antibody titers did not differ between these two groups (median = 54.6 vs 44.2 EU/ml, respectively, p = 0.4). CMV IgM titers were negative for all 16 participants, suggesting that recent primary CMV infection was unlikely. These results demonstrate a strong association between the presence of CMV DNA in peripheral monocytes and the expansion of CD8 + T cells specific for the CMV immunodominant epitope pp65 495-503. Although the sample size in this study is relatively small, these findings provide initial evidence suggesting the heterogeneity of CMV IgG-seropositive older adult population and CMV viral DNA detection in peripheral monocytes as an informative tool to better understand the relationship between chronic CMV infection and T cell immunosenescence.

KW - CMV IgG serology

KW - CMV pp65 -specific CD8 T cells

KW - Monocytic CMV DNA

KW - Older adults

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U2 - 10.1007/s11357-011-9205-9

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