Cytomegalovirus infection induces the accumulation of short-lived, multifunctional CD4+CD45RA+CD27- T cells: The potential involvement of interleukin-7 in this process

Valentina Libri, Rita I. Azevedo, Sarah E. Jackson, Diletta Di Mitri, Raskit Lachmann, Stephan Fuhrmann, Milica Vukmanovic-Stejic, Kwee Yong, Luca Battistini, Florian Kern, Maria V D Soares, Arne N. Akbar

Research output: Contribution to journalArticlepeer-review

Abstract

The relative roles that ageing and lifelong cytomegalovirus (CMV) infection have in shaping naive and memory CD4+ T-cell repertoires in healthy older people is unclear. Using multiple linear regression analysis we found that age itself is a stronger predictor than CMV seropositivity for the decrease in CD45RA+CD27+CD4+ T cells over time. In contrast, the increase in CD45RA-CD27- and CD45RA+CD27-CD4+ T cells is almost exclusively the result of CMV seropositivity, with age alone having no significant effect. Furthermore, the majority of the CD45RA-CD27- and CD45RA+CD27-CD4+ T cells in CMV-seropositive donors are specific for this virus. CD45RA+CD27-CD4+ T cells have significantly reduced CD28, interleukin-7 receptor α (IL-7Rα) and Bcl-2 expression, Akt (ser473) phosphorylation and reduced ability to survive after T-cell receptor activation compared with the other T-cell subsets in the same donors. Despite this, the CD45RA+CD27- subset is as multifunctional as the CD45RA-CD27+ and CD45RA-CD27-CD4+ T-cell subsets, indicating that they are not an exhausted population. In addition, CD45RA+CD27-CD4+ T cells have cytotoxic potential as they express high levels of granzyme B and perforin. CD4+ memory T cells re-expressing CD45RA can be generated from the CD45RA-CD27+ population by the addition of IL-7 and during this process these cells down-regulated expression of IL-7R and Bcl-2 and so resemble their counterparts in vivo. Finally we showed that the proportion of CD45RA+CD27-CD4+ T cells of multiple specificities was significantly higher in the bone marrow than the blood of the same individuals, suggesting that this may be a site where these cells are generated.

Original languageEnglish
Pages (from-to)326-339
Number of pages14
JournalImmunology
Volume132
Issue number3
DOIs
Publication statusPublished - Mar 2011

Keywords

  • Ageing
  • CD4 T cells
  • CD45RA
  • CMV
  • IL-7

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Fingerprint

Dive into the research topics of 'Cytomegalovirus infection induces the accumulation of short-lived, multifunctional CD4+CD45RA+CD27- T cells: The potential involvement of interleukin-7 in this process'. Together they form a unique fingerprint.

Cite this