Cytolytic activity of NK cells after haploidentical SCT and inhibitory effect of CD94/NKG2A on NK cells. (A) Lower lysis activity by NK cells from SCT (□) than by NK cells from healthy donor (♦). NK cells from 2 patients were tested at engraftment (no. 7) or at 1 month after SCT (no. 9). NK cytolytic activity was tested against K562 target cells (K562) and mismatched primary AML targets (AML). Similar results were obtained with recipient primary AML blast. Primary AML blasts presented both distinct mismatches; in HLA-Cw of the group 2/KIR2DL2 (no. 7) or in HLA-Cw of the group 1/KIR2DL1 (no. 9). (B) Expression of HLA-E on target cells inhibited cytotoxicity of NK cells after haploidentical SCT by CD94/NKG2A. NK cells from 2 patients were tested at 3 months (no. 10) or at 1 month after SCT (no. 9) for cytotoxicity against LCL-721-221 target (221) or against LCL transfected by HLA-E (221-AEH; B2, B4). NK cells were incubated with media alone (♦), anti-IgG2b isotype control (□), or anti-NKG2A mAb (▴). Results are representative of 3 different experiments. (C) Cytotoxicity of NK cells from haploidentical SCT against primary leukemic AML blasts was restored by blocking NKG2A. (Left) Activated NK cells from 2 patients (no. 8, no. 9) were tested at 2 months after SCT for cytotoxicity against mismatched AML blasts. Primary AML blasts presented both distinct mismatches in Bw6/KIR3DL1/Cw group1/KIR2DL1 (no. 8) or Cw group 1/KIR2DL1 (no. 9). NK cells were incubated with anti-IgG2b isotype control (□) or anti-NKG2A mAb (▴). (Right) Percentage of lysis against mismatched AML blast at different effector-target (E/T) ratio. NK cells after transplantation were incubated with anti-IgG1 isotype control (□) or anti-NKG2AmAb (▦). Results show the mean of 6 different experiments and their standard deviation.