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Increased T-bet is associated with senescence of influenza virus-specific CD8 T cells in aged humans.

Publication ,  Journal Article
Dolfi, DV; Mansfield, KD; Polley, AM; Doyle, SA; Freeman, GJ; Pircher, H; Schmader, KE; Wherry, EJ
Published in: J Leukoc Biol
June 2013

Aged individuals have increased morbidity and mortality following influenza and other viral infections, despite previous exposure or vaccination. Mouse and human studies suggest increased senescence and/or exhaustion of influenza virus-specific CD8 T cells with advanced age. However, neither the relationship between senescence and exhaustion nor the underlying transcriptional pathways leading to decreased function of influenza virus-specific cellular immunity in elderly humans are well-defined. Here, we demonstrate that increased percentages of CD8 T cells from aged individuals express CD57 and KLRG1, along with PD-1 and other inhibitory receptors, markers of senescence, or exhaustion, respectively. Expression of T-box transcription factors, T-bet and Eomes, were also increased in CD8 T cells from aged subjects and correlated closely with expression of CD57 and KLRG1. Influenza virus-specific CD8 T cells from aged individuals exhibited decreased functionality with corresponding increases in CD57, KLRG1, and T-bet, a molecular regulator of terminal differentiation. However, in contrast to total CD8 T cells, influenza virus-specific CD8 T cells had altered expression of inhibitory receptors, including lower PD-1, in aged compared with young subjects. Thus, our data suggest a prominent role for senescence and/or terminal differentiation for influenza virus-specific CD8 T cells in elderly subjects.

Duke Scholars

Published In

J Leukoc Biol

DOI

EISSN

1938-3673

Publication Date

June 2013

Volume

93

Issue

6

Start / End Page

825 / 836

Location

England

Related Subject Headings

  • Young Adult
  • T-Box Domain Proteins
  • Male
  • Influenza, Human
  • Immunology
  • Humans
  • Flow Cytometry
  • Female
  • Cellular Senescence
  • CD8-Positive T-Lymphocytes
 

Citation

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Dolfi, D. V., Mansfield, K. D., Polley, A. M., Doyle, S. A., Freeman, G. J., Pircher, H., … Wherry, E. J. (2013). Increased T-bet is associated with senescence of influenza virus-specific CD8 T cells in aged humans. J Leukoc Biol, 93(6), 825–836. https://doi.org/10.1189/jlb.0912438
Dolfi, Douglas V., Kathleen D. Mansfield, Antonio M. Polley, Susan A. Doyle, Gordon J. Freeman, Hanspeter Pircher, Kenneth E. Schmader, and E John Wherry. “Increased T-bet is associated with senescence of influenza virus-specific CD8 T cells in aged humans.J Leukoc Biol 93, no. 6 (June 2013): 825–36. https://doi.org/10.1189/jlb.0912438.
Dolfi DV, Mansfield KD, Polley AM, Doyle SA, Freeman GJ, Pircher H, et al. Increased T-bet is associated with senescence of influenza virus-specific CD8 T cells in aged humans. J Leukoc Biol. 2013 Jun;93(6):825–36.
Dolfi, Douglas V., et al. “Increased T-bet is associated with senescence of influenza virus-specific CD8 T cells in aged humans.J Leukoc Biol, vol. 93, no. 6, June 2013, pp. 825–36. Pubmed, doi:10.1189/jlb.0912438.
Dolfi DV, Mansfield KD, Polley AM, Doyle SA, Freeman GJ, Pircher H, Schmader KE, Wherry EJ. Increased T-bet is associated with senescence of influenza virus-specific CD8 T cells in aged humans. J Leukoc Biol. 2013 Jun;93(6):825–836.

Published In

J Leukoc Biol

DOI

EISSN

1938-3673

Publication Date

June 2013

Volume

93

Issue

6

Start / End Page

825 / 836

Location

England

Related Subject Headings

  • Young Adult
  • T-Box Domain Proteins
  • Male
  • Influenza, Human
  • Immunology
  • Humans
  • Flow Cytometry
  • Female
  • Cellular Senescence
  • CD8-Positive T-Lymphocytes