biostudies-literatureGleason MKNIAID NIH HHSNHLBI NIH HHSNCI NIH HHS3064-72https://www.ebi.ac.uk/biostudies/studies/S-EPMC3321868biostudies-literatureUnknown119(13)NK-cell function is regulated by the integration of signals received from activating and inhibitory receptors. Here we show that a novel immune receptor, T-cell Ig and mucin-containing domain-3 (Tim-3), is expressed on resting human NK cells and is up-regulated on activation. The NK92 NK-cell line engineered to overexpress Tim-3 showed a marked increase in IFN-γ production in the presence of soluble rhGal-9 or Raji tumor cells engineered to express Gal-9. The Tim-3(+) population of low-dose IL-12/IL-18-activated primary NK cells significantly increased IFN-γ production in response to soluble rhGal-9, Gal-9 presented by cell lines, and primary acute myelogenous leukemia (AML) targets that endogenously express Gal-9. This effect is highly specific as Tim-3 Ab blockade significantly decreasedBloodTim-3 is an inducible human natural killer cell receptor that enhances interferon gamma production in response to galectin-9.PMC3321868R01 HL55417R01 CA72669P01 CA065493R01 HL055417P30-CA77598P30 CA077598P01 AI056299R01 CA072669P01 CA111412R01 HL056067P01-CA111412-01Cooley SAMiller JSVerneris MRPanoskaltsis-Mortari AO'Brien MSBlazar BRMcCullar VGleason MKLenvik TRCichocki FHirashima MHolman CJNiki TFelices MfalseTim-3 is an inducible human natural killer cell receptor that enhances interferon gamma production in response to galectin-9.NK-cell function is regulated by the integration of signals received from activating and inhibitory receptors. Here we show that a novel immune receptor, T-cell Ig and mucin-containing domain-3 (Tim-3), is expressed on resting human NK cells and is up-regulated on activation. The NK92 NK-cell line engineered to overexpress Tim-3 showed a marked increase in IFN-γ production in the presence of soluble rhGal-9 or Raji tumor cells engineered to express Gal-9. The Tim-3(+) population of low-dose IL-12/IL-18-activated primary NK cells significantly increased IFN-γ production in response to soluble rhGal-9, Gal-9 presented by cell lines, and primary acute myelogenous leukemia (AML) targets that endogenously express Gal-9. This effect is highly specific as Tim-3 Ab blockade significantly decreased2012-01-01T00:00:00Z2012 Mar2025-04-04T21:05:11.466Z2019-03-27T00:52:04ZS-EPMC33218682232345310.1182/blood-2011-06-360321