Boelen, Lies; Debebe, Bisrat; Silveira, Marcos; Salam, Arafa; Makinde, Julia; Roberts, Chrissy H; Wang, Eddie CY; Frater, John; Gilmour, Jill; Twigger, Katie; +19 more... 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; 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-eaao2892. ISSN 2470-9468 DOI: https://doi.org/10.1126/sciimmunol.aao2892
Permanent Identifier
Use this Digital Object Identifier when citing or linking to this resource.
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 |
---|---|
Faculty and Department | Faculty of Infectious and Tropical Diseases > Dept of Clinical Research |
PubMed ID | 30413420 |
Downloads
Filename: Boelen_etal_2018_Inhibitory killer-cell.pdf
Licence: Creative Commons: Attribution-Noncommercial-No Derivative Works 3.0
DownloadFilename: Boelen_etal_2018_Inhibitory killer-cell_supplementary material.pdf
Licence: Creative Commons: Attribution-Noncommercial-No Derivative Works 3.0
Download