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Blood, 15 May 2005, Vol. 105, No. 10, pp. 4135-4142. Prepublished online as a Blood First Edition Paper on February 1, 2005; DOI 10.1182/blood-2004-10-4113. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-10-4113v1 105/10/4135    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 Nguyen, S. Articles by Vieillard, V. Search for Related Content PubMed PubMed Citation Articles by Nguyen, S. Articles by Vieillard, V. Related Collections Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION NK-cell reconstitution after haploidentical hematopoietic stem-cell transplantations: immaturity of NK cells and inhibitory effect of NKG2A override GvL effect Stephanie Nguyen, Nathalie Dhedin, Jean-Paul Vernant, Mathieu Kuentz, Ahmad Al Jijakli, Nathalie Rouas-Freiss, Edgardo D. Carosella, Ali Boudifa, Patrice Debré, and Vincent Vieillard From the Laboratoire d'Immunologie Cellulaire et Tissulaire, Institut National de la Santé et de la Recherche Médicale (INSERM) U543, Hôpital Pitié-Salpêtrière, Paris, France; the Service d'Hématologie Clinique, Hôpital Pitié-Salpêtrière, Paris, France; the Service d'Hématologie Clinique, Hôpital Henri Mondor, Créteil, France; and Connissariat a l'Energie Atomique (CEA), Hôpital Saint-Louis, Paris, France. Natural killer (NK) cell alloreactivity is reported to mediate strong GvL (graft versus leukemia) effect in patients after haploidentical stem-cell transplantation (SCT) for acute myeloid leukemia (AML). Because subsequent immune reconstitution remains a major concern, we studied NK-cell recovery in 10 patients with AML who received haplomismatched SC transplants, among whom no GvL effect was observed, despite the mismatched immunoglobulin-like receptor (KIR) ligand in the GvH direction for 8 of 10 patients. NK cells generated after SCT exhibited an immature phenotype: the cytotoxic CD3-CD56dim subset was small, expression of KIRs and NKp30 was reduced, while CD94/NKG2A expression was increased. This phenotype was associated to in vitro lower levels of cytotoxicity against a K562 cell line and against primary mismatched AML blasts than donor samples. This impaired lysis was correlated with CD94/NKG2A expression in NK cells. Blockading CD94/NKG2A restored lysis against the AML blasts, which all expressed HLA-E, the ligand for CD94/NKG2A. Our present study allows a better understanding of the NK-cell differentiation after SCT. These results revealed that the NK cells generated after haplomismatched SCT are blocked at an immature state characterized by specific phenotypic features and impaired functioning, having potential impact for immune responsiveness and transplantation outcome. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Diermayr, H. Himmelreich, B. Durovic, A. Mathys-Schneeberger, U. Siegler, U. Langenkamp, J. Hofsteenge, A. Gratwohl, A. Tichelli, M. Paluszewska, et al. NKG2D ligand expression in AML increases in response to HDAC inhibitor valproic acid and contributes to allorecognition by NK-cell lines with single KIR-HLA class I specificities Blood, February 1, 2008; 111(3): 1428 - 1436. [Abstract] [Full Text] [PDF] J. Yu, G. Heller, J. Chewning, S. Kim, W. M. Yokoyama, and K. C. Hsu Hierarchy of the Human Natural Killer Cell Response Is Determined by Class and Quantity of Inhibitory Receptors for Self-HLA-B and HLA-C Ligands J. Immunol., November 1, 2007; 179(9): 5977 - 5989. [Abstract] [Full Text] [PDF] J. S. Miller, S. Cooley, P. Parham, S. S. Farag, M. R. Verneris, K. L. McQueen, L. A. Guethlein, E. A. Trachtenberg, M. Haagenson, M. M. Horowitz, et al. Missing KIR ligands are associated with less relapse and increased graft-versus-host disease (GVHD) following unrelated donor allogeneic HCT Blood, June 1, 2007; 109(11): 5058 - 5061. [Abstract] [Full Text] [PDF] J. C. Fischer, H. Ottinger, S. Ferencik, M. Sribar, M. Punzel, D. W. Beelen, M. A. Schwan, H. Grosse-Wilde, P. Wernet, and M. Uhrberg Relevance of C1 and C2 Epitopes for Hemopoietic Stem Cell Transplantation: Role for Sequential Acquisition of HLA-C-Specific Inhibitory Killer Ig-Like Receptor J. Immunol., March 15, 2007; 178(6): 3918 - 3923. [Abstract] [Full Text] [PDF] B. Grzywacz, N. Kataria, M. Sikora, R. A. Oostendorp, E. A. Dzierzak, B. R. Blazar, J. S. Miller, and M. R. Verneris Coordinated acquisition of inhibitory and activating receptors and functional properties by developing human natural killer cells Blood, December 1, 2006; 108(12): 3824 - 3833. [Abstract] [Full Text] [PDF] S. L. Rogers, A. Rouhi, F. Takei, and D. L. Mager A Role for DNA Hypomethylation and Histone Acetylation in Maintaining Allele-Specific Expression of Mouse NKG2A in Developing and Mature NK Cells J. Immunol., July 1, 2006; 177(1): 414 - 421. [Abstract] [Full Text] [PDF] S. Cooley, V. McCullar, R. Wangen, T. L. Bergemann, S. Spellman, D. J. Weisdorf, and J. S. Miller KIR reconstitution is altered by T cells in the graft and correlates with clinical outcomes after unrelated donor transplantation Blood, December 15, 2005; 106(13): 4370 - 4376. [Abstract] [Full Text] [PDF]

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