Libri, Valentina, Azevedo, Rita I., Jackson, Sarah E., Di Mitri, Diletta, Lachmann, Raskit, Fuhrmann, Stephan, Vukmanovic-Stejic, Milica, Yong, Kwee, Battistini, Luca, Kern, Florian, Soares, Maria V. D. and Akbar, Arne N. (2011) Cytomegalovirus infection induces the accumulation of short-lived, multifunctional CD4(+) CD45RA(+) CD27(-) T cells: the potential involvement of interleukin-7 in this process. Immunology, 132 (3). pp. 326-339. ISSN 0019-2805

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Abstract

P>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 alpha (IL-7R alpha) 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.

Item Type:	Article
Schools and Departments:	Brighton and Sussex Medical School > Clinical and Experimental Medicine
Subjects:	Q Science > QR Microbiology > QR0180 Immunology
Depositing User:	Grecia GarciaGarcia
Date Deposited:	17 Aug 2011 10:35
Last Modified:	30 Nov 2012 16:55
URI:	http://srodev.sussex.ac.uk/id/eprint/7242
Google Scholar:	7 Citations

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