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

Boelen, Lies, Debebe, Bisrat, Silveira, Marcos, Salam, Arafa, Makinde, Julia, Roberts, Chrissy h., Wang, Edward, Frater, John, Gilmour, Jill, Twigger, Katie, Ladell, Kristin, Miners, Kelly L., Jayaraman, Jyothi, Traherne, James A., Price, David A., Qi, Ying, Martin, Maureen P., Macallan, Derek C., Thio, Chloe L., Astemborski, Jacquie, Kirk, Gregory, Donfield, Sharyne M., Buchbinder, Susan, Khakoo, Salim I., Goedert, James J., Trowsdale, John, Carrington, Mary, Kollnberger, Simon and Asquith, Becca 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. 10.1126/sciimmunol.aao2892

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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
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: American Association for the Advancement of Science
ISSN: 2470-9468
Date of First Compliant Deposit: 5 December 2018
Date of Acceptance: 9 October 2018
Last Modified: 20 Oct 2019 12:43
URI: http://orca.cf.ac.uk/id/eprint/117411

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