Inhibitory killer cell immunoglobulin-like receptors strengthen CD8+ T cell-mediated control of HIV-1, HCV, and HTLV-1.
Boelen L., Debebe B., Silveira M., Salam A., Makinde J., Roberts CH., Wang ECY., Frater J., Gilmour J., Twigger K., Ladell K., Miners KL., Jayaraman J., Traherne JA., Price DA., Qi Y., Martin MP., Macallan DC., Thio CL., Astemborski J., Kirk G., Donfield SM., Buchbinder S., Khakoo SI., Goedert JJ., Trowsdale J., Carrington M., Kollnberger S., Asquith B.
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.