Latent infection with cytomegalovirus is associated with poor memory CD4 responses to influenza A core proteins in the elderly

Evelyna Derhovanessian, Andrea B Maier, Karin Hähnel, Janet E McElhaney, Eline P Slagboom, Graham Pawelec

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Influenza remains a major pathogen in older people. Infection with CMV and the accumulation of late-differentiated T cells associated with it have been implicated in poor Ab responsiveness to influenza vaccination in the elderly, most of whom are CMV positive. However, whether CMV infection also affects memory T cell responses to influenza remains unknown. To investigate this, we assessed T cell responses to influenza A matrix protein and nucleoprotein ex vivo in 166 Dutch individuals (mean age 62.2 y, range 42-82) and validated the results in a second cohort from North America (mean age 73.1 y, range 65-81, n = 28). We found that less than half of the CMV-infected older subjects mounted a CD4 T cell response to influenza Ags, whereas ∼80% of uninfected elderly did so. A similar proportion of younger subjects possessed influenza A virus-responsive CD4 T cells, and, interestingly, this was the case whether they were CMV-infected. Thus, the effect of CMV was only seen in the older donors, who may have been exposed to the virus for decades. The percentage of donors with CD8 responses to influenza A virus was lower than those with CD4; this was not influenced by whether the subjects were CMV seropositive or seronegative. CMV-seropositive responders had significantly higher frequencies of late-differentiated CD4 T-cells (CD45RA(+/-)CCR7(-)CD27(-)CD28(-)) compared with CMV-infected nonresponders. These data add to the accumulating evidence that infection with CMV has profound but heterogeneous effects on responses to the products of other viruses and have implications for the design of influenza vaccines, especially in the elderly.

Original languageEnglish
Pages (from-to)3624-31
Number of pages8
JournalJournal of Immunology
Volume193
Issue number7
DOIs
Publication statusPublished - 1 Oct 2014

Fingerprint

Cytomegalovirus Infections
Human Influenza
T-Lymphocytes
Proteins
Influenza A virus
Infection
Tissue Donors
Viruses
Nucleoproteins
Influenza Vaccines
North America
Vaccination

Bibliographical note

Copyright © 2014 by The American Association of Immunologists, Inc.

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging/immunology
  • CD4-Positive T-Lymphocytes/immunology
  • CD8-Positive T-Lymphocytes/immunology
  • Cohort Studies
  • Cytomegalovirus/physiology
  • Cytomegalovirus Infections/immunology
  • Female
  • Humans
  • Immunologic Memory
  • Influenza A virus/immunology
  • Influenza Vaccines/immunology
  • Male
  • Middle Aged
  • Viral Core Proteins/immunology
  • Virus Latency/immunology

Cite this

Derhovanessian, Evelyna ; Maier, Andrea B ; Hähnel, Karin ; McElhaney, Janet E ; Slagboom, Eline P ; Pawelec, Graham. / Latent infection with cytomegalovirus is associated with poor memory CD4 responses to influenza A core proteins in the elderly. In: Journal of Immunology. 2014 ; Vol. 193, No. 7. pp. 3624-31.
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abstract = "Influenza remains a major pathogen in older people. Infection with CMV and the accumulation of late-differentiated T cells associated with it have been implicated in poor Ab responsiveness to influenza vaccination in the elderly, most of whom are CMV positive. However, whether CMV infection also affects memory T cell responses to influenza remains unknown. To investigate this, we assessed T cell responses to influenza A matrix protein and nucleoprotein ex vivo in 166 Dutch individuals (mean age 62.2 y, range 42-82) and validated the results in a second cohort from North America (mean age 73.1 y, range 65-81, n = 28). We found that less than half of the CMV-infected older subjects mounted a CD4 T cell response to influenza Ags, whereas ∼80{\%} of uninfected elderly did so. A similar proportion of younger subjects possessed influenza A virus-responsive CD4 T cells, and, interestingly, this was the case whether they were CMV-infected. Thus, the effect of CMV was only seen in the older donors, who may have been exposed to the virus for decades. The percentage of donors with CD8 responses to influenza A virus was lower than those with CD4; this was not influenced by whether the subjects were CMV seropositive or seronegative. CMV-seropositive responders had significantly higher frequencies of late-differentiated CD4 T-cells (CD45RA(+/-)CCR7(-)CD27(-)CD28(-)) compared with CMV-infected nonresponders. These data add to the accumulating evidence that infection with CMV has profound but heterogeneous effects on responses to the products of other viruses and have implications for the design of influenza vaccines, especially in the elderly.",
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author = "Evelyna Derhovanessian and Maier, {Andrea B} and Karin H{\"a}hnel and McElhaney, {Janet E} and Slagboom, {Eline P} and Graham Pawelec",
note = "Copyright {\circledC} 2014 by The American Association of Immunologists, Inc.",
year = "2014",
month = "10",
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doi = "10.4049/jimmunol.1303361",
language = "English",
volume = "193",
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Latent infection with cytomegalovirus is associated with poor memory CD4 responses to influenza A core proteins in the elderly. / Derhovanessian, Evelyna; Maier, Andrea B; Hähnel, Karin; McElhaney, Janet E; Slagboom, Eline P; Pawelec, Graham.

In: Journal of Immunology, Vol. 193, No. 7, 01.10.2014, p. 3624-31.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Latent infection with cytomegalovirus is associated with poor memory CD4 responses to influenza A core proteins in the elderly

AU - Derhovanessian, Evelyna

AU - Maier, Andrea B

AU - Hähnel, Karin

AU - McElhaney, Janet E

AU - Slagboom, Eline P

AU - Pawelec, Graham

N1 - Copyright © 2014 by The American Association of Immunologists, Inc.

PY - 2014/10/1

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N2 - Influenza remains a major pathogen in older people. Infection with CMV and the accumulation of late-differentiated T cells associated with it have been implicated in poor Ab responsiveness to influenza vaccination in the elderly, most of whom are CMV positive. However, whether CMV infection also affects memory T cell responses to influenza remains unknown. To investigate this, we assessed T cell responses to influenza A matrix protein and nucleoprotein ex vivo in 166 Dutch individuals (mean age 62.2 y, range 42-82) and validated the results in a second cohort from North America (mean age 73.1 y, range 65-81, n = 28). We found that less than half of the CMV-infected older subjects mounted a CD4 T cell response to influenza Ags, whereas ∼80% of uninfected elderly did so. A similar proportion of younger subjects possessed influenza A virus-responsive CD4 T cells, and, interestingly, this was the case whether they were CMV-infected. Thus, the effect of CMV was only seen in the older donors, who may have been exposed to the virus for decades. The percentage of donors with CD8 responses to influenza A virus was lower than those with CD4; this was not influenced by whether the subjects were CMV seropositive or seronegative. CMV-seropositive responders had significantly higher frequencies of late-differentiated CD4 T-cells (CD45RA(+/-)CCR7(-)CD27(-)CD28(-)) compared with CMV-infected nonresponders. These data add to the accumulating evidence that infection with CMV has profound but heterogeneous effects on responses to the products of other viruses and have implications for the design of influenza vaccines, especially in the elderly.

AB - Influenza remains a major pathogen in older people. Infection with CMV and the accumulation of late-differentiated T cells associated with it have been implicated in poor Ab responsiveness to influenza vaccination in the elderly, most of whom are CMV positive. However, whether CMV infection also affects memory T cell responses to influenza remains unknown. To investigate this, we assessed T cell responses to influenza A matrix protein and nucleoprotein ex vivo in 166 Dutch individuals (mean age 62.2 y, range 42-82) and validated the results in a second cohort from North America (mean age 73.1 y, range 65-81, n = 28). We found that less than half of the CMV-infected older subjects mounted a CD4 T cell response to influenza Ags, whereas ∼80% of uninfected elderly did so. A similar proportion of younger subjects possessed influenza A virus-responsive CD4 T cells, and, interestingly, this was the case whether they were CMV-infected. Thus, the effect of CMV was only seen in the older donors, who may have been exposed to the virus for decades. The percentage of donors with CD8 responses to influenza A virus was lower than those with CD4; this was not influenced by whether the subjects were CMV seropositive or seronegative. CMV-seropositive responders had significantly higher frequencies of late-differentiated CD4 T-cells (CD45RA(+/-)CCR7(-)CD27(-)CD28(-)) compared with CMV-infected nonresponders. These data add to the accumulating evidence that infection with CMV has profound but heterogeneous effects on responses to the products of other viruses and have implications for the design of influenza vaccines, especially in the elderly.

KW - Adult

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KW - Aging/immunology

KW - CD4-Positive T-Lymphocytes/immunology

KW - CD8-Positive T-Lymphocytes/immunology

KW - Cohort Studies

KW - Cytomegalovirus/physiology

KW - Cytomegalovirus Infections/immunology

KW - Female

KW - Humans

KW - Immunologic Memory

KW - Influenza A virus/immunology

KW - Influenza Vaccines/immunology

KW - Male

KW - Middle Aged

KW - Viral Core Proteins/immunology

KW - Virus Latency/immunology

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