| Literature DB >> 30413420 |
Lies Boelen1, Bisrat Debebe1, Marcos Silveira1,2, Arafa Salam3, Julia Makinde4, Chrissy H Roberts5, Eddie C Y Wang6, John Frater7,8, Jill Gilmour4, Katie Twigger1, Kristin Ladell6, Kelly L Miners6, Jyothi Jayaraman9, James A Traherne9, David A Price6, Ying Qi10, Maureen P Martin10, Derek C Macallan3, Chloe L Thio11, Jacquie Astemborski11, Gregory Kirk11, Sharyne M Donfield12, Susan Buchbinder13, Salim I Khakoo14, James J Goedert15, John Trowsdale9, Mary Carrington10,16, Simon Kollnberger6, Becca Asquith17.
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.Entities:
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Year: 2018 PMID： 30413420 PMCID： PMC6277004 DOI： 10.1126/sciimmunol.aao2892
Source DB: PubMed Journal: Sci Immunol ISSN： 2470-9468