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Blood, 15 November 2005, Vol. 106, No. 10, pp. 3666-3672.
Prepublished online as a Blood First Edition Paper on July 26, 2005; DOI 10.1182/blood-2005-02-0479.
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Submitted February 4, 2005
Accepted July 18, 2005
The antileukemia effect of HLA-matched NK and NK-T cells in chronic myelogenous leukemia involves NKG2D-target cell interaction
Giuseppe Sconocchia, Michelle Lau, Maurizio Provenzano, Katayoun Rezvani, Wachanan Wongsena, Hiroshi Fujiwara, Nancy Hensel, Jos Melenhorst, Jonming Li, Soldano Ferrone, and John Barrett*
Stem Cell Allotransplantation Section, Hematology Branch, National Heart Lung and Blood Institute, National Institutes of Health (NIH), Bethesda, MD, USA
Molecular Immunology Section, Department of Transfusion Medicine, Clinical Center, NIH, Bethesda, MD, USA
Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, USA
* Corresponding author; email: barrettj{at}nhlbi.nih.gov.
To study natural killer (NK) cell mediated antileukemic activity in chronic myelogenous leukemia (CML) we investigated the ability of HLA-matched and mismatched CD56+ cells to inhibit CFU-GM formation by leukemic CD34+ cells. In 14 HLA-identical donor-recipient pairs, donor CD56+ cells inhibited CML CFU-GM comparably to effectors from 14 HLA-mismatched unrelated individuals (mean inhibition 42±9% vs 39.5±7% at a 10:1 E:T ratio), suggesting that KIR incompatibility was not essential for an anti-leukemic effect. Both CD56+CD3- (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 MICA/B on CML CD34 cells and their ability to bind the NK activation ligand NKG2D. However in vivo, CML cells may avoid NK cell mediated immune destruction by immune escape, shedding MICA into the plasma, thereby downregulating NKG2D on CML CD56+ cells.
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