Alloreactivity of Natural Killer Cell Clones Against Childhood Precursor-B Lymphoblastic Leukemia Cells Is Determined by Differential KIR Expression.

Relapse after allogeneic stem cell transplantation of patients with acute lymphoblastic leukemia (ALL) remains a major problem. A beneficial impact of alloreactive NK cells has been reported for myeloid malignancies, but has been questionable for B-lineage-ALL. Here we show that the majority of NK cell clones from healthy donors could effectively lyse primary blasts from a representative childhood precurser-B-ALL and demonstrate the relevance of differential surface expression of KIRs (killer cell immunglobulin like receptors CD158a, CD158b and CD158e) for antileukemic alloreactivity. More than 79% of clones exerted specific lysis >40% against primary ALL blasts. Mismatch of effector/target HLA-C type (KIR-ligand incompatibility) did not correlate with antileukemic alloreactivity, although non-malignant lymphoblastoid cell lines were lysed according to KIR-ligand incompatibility. In contrast differential surface expression of the three major KIRs showed significant impact on the antileukemic activity against precursor-B-ALL blasts. NK clones with none of the three KIRs or a single KIR that recognized no ligand, were not inhibited by the targets and exerted higher lysis (p = <0.03) in comparison to NK clones with expression of one or more KIRs with a ligand on the ALL blasts. In conclusion the differential surface expression of KIRs is relevant to predict NK cell activity against childhood lymphoid leukemia.