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Blood, 15 October 2008, Vol. 112, No. 8, pp. 3488-3499. Prepublished online as a Blood First Edition Paper on July 21, 2008; DOI 10.1182/blood-2007-07-103325. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-07-103325v1 112/8/3488    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Vago, L. Articles by Fleischhauer, K. Search for Related Content PubMed PubMed Citation Articles by Vago, L. Articles by Fleischhauer, K. Related Collections Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Temporal, quantitative, and functional characteristics of single-KIR–positive alloreactive natural killer cell recovery account for impaired graft-versus-leukemia activity after haploidentical hematopoietic stem cell transplantation Luca Vago1,2, Barbara Forno1,2, Maria Pia Sormani3, Roberto Crocchiolo2, Elisabetta Zino1,4, Simona Di Terlizzi1,4, Maria Teresa Lupo Stanghellini2, Benedetta Mazzi4, Serena K. Perna2,5, Attilio Bondanza5, Derek Middleton6, Alessio Palini4, Massimo Bernardi2, Rosa Bacchetta1, Jacopo Peccatori2, Silvano Rossini4, Maria Grazia Roncarolo1,7, Claudio Bordignon7,8, Chiara Bonini5, Fabio Ciceri2, and Katharina Fleischhauer1,4 1 San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET) and 2 Hematology and Bone Marrow Transplantation Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), H San Raffaele, Milano, Italy; 3 Dipartimento di Scienze della Salute (DISSAL), Università degli Studi di Genova, Genova, Italy; 4 HLA Tissue Typing, Immunohematology and Transfusion Medicine Service and 5 Cancer Immunotherapy and Gene Therapy Program, IRCCS, H San Raffaele, Milano, Italy; 6 Northern Ireland Histocompatibility and Immunogenetics Laboratory, Belfast City Hospital, Belfast, United Kingdom; 7 University Vita-Salute San Raffaele, Milano, Italy; and 8 MolMed, Milano, Italy In this study, we have characterized reconstitution of the natural killer (NK) cell repertoire after haploidentical CD34+ selected hematopoietic stem cell transplantation (HSCT) for high-risk hematologic malignancies. Analysis focused on alloreactive single-KIR+ NK cells, which reportedly are potent antileukemic effectors. One month after HSCT, CD56bright/CD56dim NK-cell subsets showed inverted ratio and phenotypic features. CD25 and CD117 down-regulation on CD56bright, and NKG2A and CD62L up-regulation on CD56dim, suggest sequential CD56bright-to-CD56dim NK-cell maturation in vivo. Consistently, the functional potential of these maturation intermediates against leukemic blasts was impaired. Mature receptor repertoire reconstitution took at least 3 months. Importantly, at this time point, supposedly alloreactive, single-KIR+ NK cells were not yet fully functional. Frequency of these cells was highly variable, independently from predicted NK alloreactivity, and below 1% of NK cells in 3 of 6 alloreactive patients studied. In line with these observations, no clinical benefit of predicted NK alloreactivity was observed in the total cohort of 56 patients. Our findings unravel the kinetics, and limits, of NK-cell differentiation from purified haploidentical hematopoietic stem cells in vivo, and suggest that NK-cell antileukemic potential could be best exploited by infusion of mature single-KIR+ NK cells selected from an alloreactive donor. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Yu, J. M. Venstrom, X.-R. Liu, J. Pring, R. S. Hasan, R. J. O'Reilly, and K. C. Hsu Breaking tolerance to self, circulating natural killer cells expressing inhibitory KIR for non-self HLA exhibit effector function after T cell-depleted allogeneic hematopoietic cell transplantation Blood, April 16, 2009; 113(16): 3875 - 3884. [Abstract] [Full Text] [PDF]

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