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Inhibitory killer-cell immunoglobulin-like receptors strengthen CD8+ T cell-mediated control of HIV-1, HCV and HTLV-1

Boelen, L; Debebe, B; Silveira, M; Salam, A; Makinde, J; Roberts, C; Wang, E; Frater, J; Gilmour, J; Twigger, K; et al. Boelen, L; Debebe, B; Silveira, M; Salam, A; Makinde, J; Roberts, C; Wang, E; Frater, J; Gilmour, J; Twigger, K; Ladell, K; Miners, K; Jayaraman, J; Traherne, J; Price, D; Qi, Y; Martin, M; Macallan, DC; IAVI Protocol C Investigators; Thio, C; Astemborski, J; Kirk, G; Donfield, S; Buchbinder, S; Khakoo, S; Goedert, J; Trowsdale, J; Carrington, M; Kollnberger, S; Asquith, B (2018) Inhibitory killer-cell immunoglobulin-like receptors strengthen CD8+ T cell-mediated control of HIV-1, HCV and HTLV-1. Science Immunology, 3 (29). eaao2892. ISSN 2470-9468 https://doi.org/10.1126/sciimmunol.aao2892
SGUL Authors: Macallan, Derek Clive

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Abstract

Killer cell immunoglobulin-like receptors (KIRs) are expressed predominantly on natural killer cells, where they play a key role in the regulation of innate immune responses. Recent studies show that inhibitory KIRs can also affect adaptive T cell–mediated immunity. In mice and in human T cells in vitro, inhibitory KIR ligation enhanced CD8+ T cell survival. To investigate the clinical relevance of these observations, we conducted an extensive immunogenetic analysis of multiple independent cohorts of HIV-1–, hepatitis C virus (HCV)–, and human T cell leukemia virus type 1 (HTLV-1)–infected individuals in conjunction with in vitro assays of T cell survival, analysis of ex vivo KIR expression, and mathematical modeling of host-virus dynamics. Our data suggest that functional engagement of inhibitory KIRs enhances the CD8+ T cell response against HIV-1, HCV, and HTLV-1 and is a significant determinant of clinical outcome in all three viral infections.

Item Type: Article
Additional Information: This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science Immunology on Vol 3, 9 Nov 2018, DOI: 10.1126/sciimmunol.aao2892.
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Science Immunology
ISSN: 2470-9468
Dates:
DateEvent
9 November 2018Published
10 October 2018Accepted
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
103865Z/14/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
J007439Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G1001052Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
317040Seventh Framework Programmehttp://dx.doi.org/10.13039/501100004963
15012Leukemia and Lymphoma ResearchUNSPECIFIED
206435/2014‐2Brazilian National Council for Scientific DevelopmentUNSPECIFIED
105609/Z/14/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
090323/Z/09/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
MR/L018373/LMedical Research Councilhttp://dx.doi.org/10.13039/501100000265
MR/P001602/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
695551European Research Councilhttp://dx.doi.org/10.13039/501100000781
R01 DA13324National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
100326Z/12/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
MR/M019829/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
R01‐HD‐41224National Institute of Child Health and Human Developmenthttp://dx.doi.org/10.13039/100000071
U01‐DA‐036297National Institute on Drug Abusehttp://dx.doi.org/10.13039/100000026
R01‐DA‐12568National Institute on Drug Abusehttp://dx.doi.org/10.13039/100000026
K24‐AI118591National Institute on Drug Abusehttp://dx.doi.org/10.13039/100000026
URI: https://openaccess.sgul.ac.uk/id/eprint/110261
Publisher's version: https://doi.org/10.1126/sciimmunol.aao2892

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