Inhibitory killer cell immunoglobulin-like receptors strengthen CD8+ T cell-mediated control of HIV-1, HCV, and HTLV-1.
Miners, Kelly L
Donfield, Sharyne M
American Association for the Advancement of Science (AAAS)
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Boelen, L., Debebe, B., Silveira, M., Salam, A., Makinde, J., Roberts, C. H., Wang, E. C., et al. (2018). Inhibitory killer cell immunoglobulin-like receptors strengthen CD8+ T cell-mediated control of HIV-1, HCV, and HTLV-1.. Sci Immunol, 3 (29) https://doi.org/10.1126/sciimmunol.aao2892
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.
CD8-Positive T-Lymphocytes, Humans, Hepacivirus, Human T-lymphotropic virus 1, HIV-1, Receptors, KIR
European Research Council (695551)
Medical Research Council (G0901682)
MRC (via University College London (UCL)) (15012)
External DOI: https://doi.org/10.1126/sciimmunol.aao2892
This record's URL: https://www.repository.cam.ac.uk/handle/1810/286350