To study natural killer (NK) cell-mediated antileukemic activity in chronic myelogenous leukemia (CIVIL), we investigated the ability of HLA-matched and mismatched CD56(+) cells to inhibit granulocyte macrophage-colony-forming unit (CFU-GM) formation by leukemic CD34(+) cells. In 14 HLA-identical donor-recipient pairs, donor CD56(+) cells inhibited CIVIL CFU-GM comparably to effectors from 14 HLA-mismatched unrelated individuals (mean inhibition 42% +/- 9% vs 39.5% +/- 7% at a 10:1 effector-to-target (E/T) ratio), suggesting that killer inhibitory receptor (KIR) incompatibility was not essential for an antileukemic effect. Both CD56(+)CD3(-) (natural killer [NK]) and CD56(+)CD3(+)(NK-T) cells inhibited CFU-GM growth of CML but not normal CD34(+) cells. A mechanism for this leukemia-specific cytotoxicity was suggested by the abnormal overexpression of major histocompatibility class I chain-related gene A or gene B (MICA/B) on CIVIL CD34 cells and their ability to bind the NK activation ligand NKG2D. However, in vivo, CIVIL cells may avoid NK-cell-mediated immune destruction by immune escape, shedding MICA into the plasma, thereby down-regulating NKG2D on CIVIL CD56(+) cells.
The antileukemia effect of HLA-matched NK and NK-T cells in chronic myelogenous leukemia involves NKG2D-target-cell interactions
Sconocchia G;
2005
Abstract
To study natural killer (NK) cell-mediated antileukemic activity in chronic myelogenous leukemia (CIVIL), we investigated the ability of HLA-matched and mismatched CD56(+) cells to inhibit granulocyte macrophage-colony-forming unit (CFU-GM) formation by leukemic CD34(+) cells. In 14 HLA-identical donor-recipient pairs, donor CD56(+) cells inhibited CIVIL CFU-GM comparably to effectors from 14 HLA-mismatched unrelated individuals (mean inhibition 42% +/- 9% vs 39.5% +/- 7% at a 10:1 effector-to-target (E/T) ratio), suggesting that killer inhibitory receptor (KIR) incompatibility was not essential for an antileukemic effect. Both CD56(+)CD3(-) (natural killer [NK]) and CD56(+)CD3(+)(NK-T) cells inhibited CFU-GM growth of CML but not normal CD34(+) cells. A mechanism for this leukemia-specific cytotoxicity was suggested by the abnormal overexpression of major histocompatibility class I chain-related gene A or gene B (MICA/B) on CIVIL CD34 cells and their ability to bind the NK activation ligand NKG2D. However, in vivo, CIVIL cells may avoid NK-cell-mediated immune destruction by immune escape, shedding MICA into the plasma, thereby down-regulating NKG2D on CIVIL CD56(+) cells.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
