UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Differing HLA types influence inhibitory receptor signalling in CMV-specific CD8+ T cells.

Macaulay, R; Riddell, NE; Griffiths, SJ; Akbar, AN; Henson, SM; (2013) Differing HLA types influence inhibitory receptor signalling in CMV-specific CD8+ T cells. Human Immunology , 74 (3) 302 - 309. 10.1016/j.humimm.2012.11.014. Green open access

[thumbnail of 1392572.pdf]
Preview
PDF
1392572.pdf

Download (916kB)

Abstract

The dysregulated immune response to CMV constitutes a major force driving T cell immunosenescence and growing evidence suggests that it is not a benign virus in old age. We show here that the PD-1/L pathway defines a reversible defect in CMV specific CD8(+) T cell proliferative responses in both young and old individuals. More specifically, highly differentiated CD45RA(+)CD27(-) CMV-specific CD8(+) T cells exhibit a proliferative deficit compared their central and effector memory counterparts, which is reversed following PD-L blockade. However, we also report that HLA-B(∗)07/TPR specific CD8(+) T cells express higher levels of PD-1 than HLA-A(∗)02/NLV specific cells and HLA-A(∗)02 individuals show a higher proliferative response to PD-L blockade, than HLA-B(∗)07 individuals, which we postulate may be due to the differing functional avidities for these two CMV-specific CD8(+) T cells populations. Nevertheless data presented here demonstrate that CMV-specific CD8(+) T cells can be functionally enhanced by perturbation of the PD-1/L signalling pathway, whose manipulation may provide a therapeutic modality to combat age-associated immune decline.

Type: Article
Title: Differing HLA types influence inhibitory receptor signalling in CMV-specific CD8+ T cells.
Location: US
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.humimm.2012.11.014
Publisher version: http://dx.doi.org/10.1016/j.humimm.2012.11.014
Language: English
Additional information: This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1392572
Downloads since deposit
264Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item