Rudimentary signs of immunosenescence in Cytomegalovirus-seropositive healthy young adults

James E Turner, John P Campbell, Kate M Edwards, Lauren J Howarth, Graham Pawelec, Sarah Aldred, Paul Moss, Mark T Drayson, Victoria E Burns, Jos A Bosch

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

Abstract

Ageing is associated with a decline in immune competence termed immunosenescence. In the elderly, this process results in an accumulation of differentiated 'effector' phenotype memory T cells, predominantly driven by Cytomegalovirus (CMV) infection. Here, we asked whether CMV also drives immunity towards a senescent profile in healthy young adults. One hundred and fifty-eight individuals (mean ± SD; age 21 ± 3 years, body mass index 22.7 ± 2.7 kg m(2)) were assessed for CMV serostatus, the numbers/proportions of CD4(+) and CD8(+) late differentiated/effector memory cells (i.e. CD27(-)CD28(-)/CD45RA(+)), plasma interleukin-6 (IL-6) and antibody responses to an in vivo antigen challenge (half-dose influenza vaccine). Thirty percent (48/158) of participants were CMV(+). A higher lymphocyte and CD8(+) count (both p < 0.01) and a lower CD4/CD8 ratio (p < 0.03) were observed in CMV(+) people. Eight percent (4/58) of CMV(+) individuals exhibited a CD4/CD8 ratio <1.0, whereas no CMV(-) donor showed an inverted ratio (p < 0.001). The numbers of CD4(+) and CD8(+)CD27(-)CD28(-)/CD45RA(+) cells were ~ fourfold higher in CMV(+) people (p < 0.001). Plasma IL-6 was higher in CMV(+) donors (p < 0.05) and showed a positive association with the numbers of CD8(+)CD28(-) cells (p < 0.03). Finally, there was a significant negative correlation between vaccine-induced antibody responses to the A/Brisbane influenza strain and CMV-specific immunoglobulin G titres (p < 0.05). This reduced vaccination response was associated with greater numbers of total CD8(+) and CD4(+) and CD8(+)CD27(-)CD28(-)/CD45RA(+) cells (p < 0.05). This study observed marked changes in the immune profile of young adults infected with CMV, suggesting that this virus may underlie rudimentary aspects of immunosenescence even in a chronologically young population.

Original languageEnglish
Pages (from-to)287-97
Number of pages11
JournalAge (Dordrecht, Netherlands)
Volume36
Issue number1
DOIs
Publication statusPublished - Feb 2014

Keywords

  • Aging
  • Antibodies, Viral
  • CD4-CD8 Ratio
  • Cytomegalovirus
  • Cytomegalovirus Infections
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Humans
  • Immunoglobulin G
  • Immunophenotyping
  • Influenza Vaccines
  • Interleukin-6
  • Male
  • Young Adult

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