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Blood, Vol. 94 No. 1 (July 1), 1999:
pp. 333-339
Role of Natural Killer Cell Alloreactivity in HLA-Mismatched
Hematopoietic Stem Cell Transplantation
Loredana Ruggeri,
Marusca Capanni,
Myriam Casucci,
Isabella Volpi,
Antonella Tosti,
Katia Perruccio,
Elena Urbani,
Robert S. Negrin,
Massimo F. Martelli, and
Andrea Velardi
From the Division of Hematology and Clinical Immunology, the
Department of Clinical and Experimental Medicine, University of
Perugia, Perugia, Italy; and the Division of Bone Marrow
Transplantation, the Department of Medicine, Stanford University,
Stanford, CA 94305.
Because of the expression of inhibitory receptors (KIR) for major
histocompatibility complex (MHC) class I allotypes, a person's natural
killer (NK) cells will not recognize and will, therefore, kill cells
from individuals lacking his/her KIR epitopes. This study investigated
the role of NK cell alloreactivity in human HLA haplotype-mismatched
hematopoietic stem cell transplantation and, specifically, the role of
the three major NK specificities, ie, those for HLA-C group 1, HLA-C
group 2, and HLA-Bw4 alleles. In 20 of 60 donor-recipient pairs, KIR
epitope incompatibility and functional analyses of donor NK cell clones
predicted donor NK cells could cause graft-versus-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 recipient's target cells. Lysis followed the rules of NK cell alloreactivity, being blocked only by the MHC class I KIR epitope which
was missing in the recipient. The alloreactive NK clones also killed
the allogeneic leukemia. Transplants from these KIR epitope
incompatible donors had higher engraftment rates. Therefore, a GVL
effector and engraftment facilitating mechanism, which is independent
of T-cell-mediated GVH reactions, may be operational in HLA mismatched
hematopoietic cell transplants.
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