Premium
Cytomegalovirus infection induces the accumulation of short‐lived, multifunctional CD4 + CD45RA + CD27 − T cells: the potential involvement of interleukin‐7 in this process
Author(s) -
Libri Valentina,
Azevedo Rita I.,
Jackson Sarah E.,
Di Mitri Diletta,
Lachmann Raskit,
Fuhrmann Stephan,
VukmanovicStejic Milica,
Yong Kwee,
Battistini Luca,
Kern Florian,
Soares Maria V. D.,
Akbar Arne N.
Publication year - 2011
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2010.03386.x
Subject(s) - granzyme b , cd8 , cd28 , population , cytotoxic t cell , biology , t cell , perforin , immunology , immune system , microbiology and biotechnology , in vitro , medicine , biochemistry , environmental health
Summary 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.