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Related Collections Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Robinson, K. Mistry, H. McWilliam, R. Lopez, and S. G. E. Marsh IPD--the Immuno Polymorphism Database Nucleic Acids Res., October 29, 2009; (2009) gkp879v1. [Abstract] [Full Text] [PDF] M. J. J. Rose, A. G. Brooks, L. A. Stewart, T. H. Nguyen, and A. P. Schwarer Killer Ig-Like Receptor Ligand Mismatch Directs NK Cell Expansion In Vitro J. Immunol., October 1, 2009; 183(7): 4502 - 4508. [Abstract] [Full Text] [PDF] F. Romagne, P. Andre, P. Spee, S. Zahn, N. Anfossi, L. Gauthier, M. Capanni, L. Ruggeri, D. M. Benson Jr, B. W. Blaser, et al. 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