Role of natural killer cell alloreactivity in HLA-mismatched hematopoieticstem cell transplantation

Because of the expression of inhibitory receptors (KIR) for major histocomp atibility complex (MHC) class I allotypes, a person's natural killer (NK) c ells will not recognize and will, therefore, kill cells from individuals la cking his/her KIR epitopes. This study investigated the role of NK cell all oreactivity in human HLA haplotype-mismatched hematopoietic stem cell trans plantation and, specifically, the role Of the three major NK specificities, ie, those for HLA-C group lr HLA-C group 2, and HLA-Bw4 alleles, In 20 of 60 donor-recipient pairs, KIR epitope incompatibility and functional analys es of donor NK cell clones predicted donor NK cells could cause graft-versu s-host (GVH)/graft-versus-leukemia (GVL) reactions. NK cell clones of donor origin were obtained from transplanted recipients and tested for lysis of recipient's cryopreserved pretransplant lymphocytes. Despite the absence of GVH disease, we detected high frequencies of NK clones which killed recipi ent's target cells. Lysis followed the rules of NK cell alloreactivity, bei ng blocked only by the MHC class I KIR epitope which was missing in the rec ipient. The alloreactive NK clones also killed the allogeneic leukemia. Tra nsplants from these KIR epitope incompatible donors had higher engraftment rates. Therefore, a GVL effector and engraftment facilitating mechanism, wh ich is independent of T-cell-mediated GVH reactions, may be operational in HLA mismatched hematopoietic cell transplants. (C) 1999 by The American Soc iety of Hematology.