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Blood, 26 March 2009, Vol. 113, No. 13, pp. 3119-3129. Prepublished online as a Blood First Edition Paper on October 22, 2008; DOI 10.1182/blood-2008-06-164103. This Article Full Text (PDF) Supplemental Table and Figure All Versions of this Article: blood-2008-06-164103v1 113/13/3119    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Pende, D. Articles by Moretta, A. Search for Related Content PubMed PubMed Citation Articles by Pende, D. Articles by Moretta, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 26, 2008 Accepted September 29, 2008 Anti-leukemia activity of alloreactive NK cells in KIR ligand-mismatched haploidentical HSCT for pediatric patients: evaluation of the functional role of activating KIR and re-definition of inhibitory KIR specificity Daniela Pende*, Stefania Marcenaro, Michela Falco, Stefania Martini, Maria Ester Bernardo, Daniela Montagna, Elisa Romeo, Celine Cognet, Miryam Martinetti, Rita Maccario, Maria Cristina Mingari, Eric Vivier, Lorenzo Moretta, Franco Locatelli, and Alessandro Moretta Immunologia, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy Dipartimento di Medicina Sperimentale, Universita di Genova, Genoa, Italy Immunologia Clinica e Sperimentale, Istituto Giannina Gaslini, Genoa, Italy Oncoematologia Pediatrica, Dipartimento di Scienze Pediatriche, Fondazione IRCCS Policlinico San Matteo, Universita di Pavia, Pavia, Italy Centre d’Immunologie de Marseille-Luminy, Universite de la Mediteranee, Marseille, France Laboratorio di Tipizzazione Tissutale, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy Laboratorio di Ricerca "Trapianto di Midollo Osseo e Oncoematologia Pediatrica", Fondazione IRCCS Policlinico San Matteo, Pavia, Italy Centro di Eccellenza per la Ricerca Biomedica, Universita di Genova, Genoa, Italy * Corresponding author; email: daniela.pende{at}istge.it. We analyzed 21 children with leukemia receiving haploidentical hematopoietic stem cell transplantation (haplo-HSCT) from KIR ligand-mismatched donors. We showed that, in most transplanted patients, variable proportions of donor-derived alloreactive NK cells displaying anti-leukemia activity were generated and maintained even late after transplantation. This was assessed through analysis of donor KIR genotype, as well as through phenotypic and functional analyses of NK cells, both at the polyclonal and clonal level. Donor-derived KIR2DL1+ NK cells isolated from the recipient displayed the expected capability of selectively killing C1/C1 target cells, including patient leukemia blasts. Differently, KIR2DL2/3+ NK cells displayed poor alloreactivity against leukemia cells carrying HLA alleles belonging to C2 group. Unexpectedly, this was due to recognition of C2 by KIR2DL2/3, as revealed by receptor blocking experiments and by binding assays of soluble KIR to HLA-C transfectants. Remarkably, however, C2/C2 leukemia blasts were killed by KIR2DL2/3+ (or by NKG2A+) NK cells that co-expressed KIR2DS1. This could be explained by the ability of KIR2DS1 to directly recognize C2 on leukemia cells. A role of the KIR2DS2 activating receptor in leukemia cell lysis could not be demonstrated. Altogether, these results may have important clinical implications for the selection of optimal donors for haplo-HSCT. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Marcenaro, C. Cantoni, S. Pesce, C. Prato, D. Pende, S. Agaugue, L. Moretta, and A. Moretta Uptake of CCR7 and acquisition of migratory properties by human KIR+ NK cells interacting with monocyte-derived DC or EBV cell lines: regulation by KIR/HLA-class I interaction Blood, November 5, 2009; 114(19): 4108 - 4116. [Abstract] [Full Text] [PDF]

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