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

Libri, V, Azevedo, R I, Jackson, S E, Di Mitri, D, Lachmann, R, Fuhrmann, S, Vukmanovic-Stejic, M, Yong, K, Battistini, L, Kern, F, Soares, M V and Akbar, A 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

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-7Ralpha) 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(-) D27+ 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
Keywords: Adult; Aged, 80 and over Aging/*immunology Antigens, CD27/biosynthesis Antigens, CD45/biosynthesis CD4-Positive T-Lymphocytes/*immunology/pathology/virology Cell Differentiation/immunology Cell Separation Cell Survival Cytomegalovirus Infections/*immunology/pathology Flow Cytometry Humans Interleukin-7/*physiology Middle Aged Signal Transduction/immunology T-Lymphocyte Subsets/*immunology/pathology Young Adult
Schools and Departments: Brighton and Sussex Medical School > Clinical Medicine
Subjects: Q Science > QR Microbiology > QR0180 Immunology
Depositing User: Florian Kern
Date Deposited: 23 Oct 2012 14:46
Last Modified: 23 Oct 2012 14:46
URI: http://sro.sussex.ac.uk/id/eprint/41292
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