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

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

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.

2470-9468
Boelen, Lies
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Debebe, Bisrat
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Silveira, Marcos
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Salam, Arafa
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Makinde, Julia
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Roberts, Chrissy H.
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Wang, Eddie C.Y.
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Frater, John
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Gilmour, Jill
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Twigger, Katie
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Ladell, Kristin
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Miners, Kelly L.
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Jayaraman, Jyothi
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Traherne, James A.
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Price, David A.
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Qi, Ying
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Martin, Maureen P.
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Macallan, Derek C.
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Thio, Chloe L.
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Astemborski, Jacquie
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Kirk, Gregory
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Donfield, Sharyne M.
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Buchbinder, Susan
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Khakoo, Salim I.
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Goedert, James J.
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Trowsdale, John
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Carrington, Mary
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Kollnberger, Simon
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Asquith, Becca
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Boelen, Lies
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Debebe, Bisrat
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Silveira, Marcos
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Salam, Arafa
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Makinde, Julia
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Roberts, Chrissy H.
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Wang, Eddie C.Y.
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Frater, John
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Gilmour, Jill
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Twigger, Katie
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Ladell, Kristin
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Miners, Kelly L.
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Jayaraman, Jyothi
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Traherne, James A.
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Price, David A.
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Qi, Ying
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Martin, Maureen P.
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Macallan, Derek C.
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Thio, Chloe L.
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Astemborski, Jacquie
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Kirk, Gregory
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Donfield, Sharyne M.
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Buchbinder, Susan
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Khakoo, Salim I.
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Goedert, James J.
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Trowsdale, John
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Carrington, Mary
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Kollnberger, Simon
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Asquith, Becca
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Boelen, Lies, Debebe, Bisrat, Silveira, Marcos, Salam, Arafa, Makinde, Julia, Roberts, Chrissy H., Wang, Eddie C.Y., 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), [eaa02892]. (doi:10.1126/sciimmunol.aao2892).

Record type: Article

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.

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Accepted/In Press date: 9 October 2018
e-pub ahead of print date: 9 November 2018
Published date: 30 November 2018
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Identifiers

Local EPrints ID: 425457
URI: http://eprints.soton.ac.uk/id/eprint/425457
DOI: doi:10.1126/sciimmunol.aao2892
ISSN: 2470-9468
PURE UUID: 3e9ba608-7a56-4dda-9472-f6e47a95aea8
ORCID for Salim I. Khakoo: ORCID iD orcid.org/0000-0002-4057-9091

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Date deposited: 19 Oct 2018 16:30
Last modified: 06 Jun 2024 04:02

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Contributors

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

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