Moreover, we show that stimulation of Tim-3+ NK cells by Gal-9 leads to NK cell activation and Tim-3 downregulation in vitro. Our data suggest that persistent signaling through Tim-3 on NK cells might result in loss of functionality and accumulation of a Tim-3low NK cell population in vivo, thereby contributing to the previously described impaired activity of NK cells in chronic HIV-1 infection. This evidence concerns the gene LGALS9 and HIV-1 infection.