Artículos de revistas
Inhibitory killer cell immunoglobulin-like receptors strengthen CD8+ T cell–mediated control of HIV-1, HCV, and HTLV-1
Fecha
2018-01-01Registro en:
Science Immunology, v. 3, n. 29, 2018.
2470-9468
10.1126/sciimmunol.aao2892
2-s2.0-85056420369
8286209184527011
Autor
Imperial College London
Universidade Estadual Paulista (Unesp)
University of London
International AIDS Vaccine Initiative Human Immunology Laboratory
London School of Hygiene and Tropical Medicine
Cardiff University School of Medicine
University of Oxford
Oxford NIHR Biomedical Research Centre
University of Cambridge
Frederick National Laboratory for Cancer Research
Johns Hopkins University
Rho
San Francisco Department of Public Health
University of Southampton
National Cancer Institute
MIT and Harvard
Institución
Resumen
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.