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

Boelen, LORCID logo; Debebe, BORCID logo; Silveira, M; Salam, A; Makinde, JORCID logo; Roberts, CHORCID logo; Wang, ECORCID logo; Frater, JORCID logo; Gilmour, J; Twigger, K; +19 more...Ladell, KORCID logo; Miners, KL; Jayaraman, J; Traherne, JAORCID logo; Price, DAORCID logo; Qi, Y; Martin, MPORCID logo; Macallan, DCORCID logo; Thio, CLORCID logo; Astemborski, J; Kirk, GORCID logo; Donfield, SM; Buchbinder, S; Khakoo, SIORCID logo; Goedert, JJORCID logo; Trowsdale, J; Carrington, MORCID logo; Kollnberger, SORCID logo; Asquith, BORCID logo and (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: 10.1126/sciimmunol.aao2892
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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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