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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3824-3833. Prepublished online as a Blood First Edition Paper on August 10, 2006; DOI 10.1182/blood-2006-04-020198. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-04-020198v1 108/12/3824    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 Grzywacz, B. Articles by Verneris, M. R. Search for Related Content PubMed PubMed Citation Articles by Grzywacz, B. Articles by Verneris, M. R. Related Collections Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Coordinated acquisition of inhibitory and activating receptors and functional properties by developing human natural killer cells Bartosz Grzywacz, Nandini Kataria, Magdalena Sikora, Robert A. Oostendorp, Elaine A. Dzierzak, Bruce R. Blazar, Jeffrey S. Miller, and Michael R. Verneris From the Departments of Pediatrics and Medicine, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis; III Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technical University Munich, Germany; the Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands; and Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland. The stages of human natural killer (NK) cell differentiation are not well established. Culturing CD34+ progenitors with interleukin 7 (IL-7), IL-15, stem cell factor (SCF), FLT-3L, and murine fetal liver cell line (EL08.1D2), we identified 2 nonoverlapping subsets of differentiating CD56+ cells based on CD117 and CD94 (CD117highCD94– and CD117low/–CD94+ cells). Both populations expressed CD161 and NKp44, but differed with respect to NKp30, NKp46, NKG2A, NKG2C, NKG2D, CD8, CD16, and KIR. Only the CD117low/– CD94+ population displayed cytotoxicity and interferon- production. Both populations arose from a single CD34+CD38– Lin– cell and their percentages changed over time in a reciprocal fashion, with CD117highCD94– cells predominating early and decreasing due to an increase of the CD117low/–CD94+ population. These 2 subsets represent distinct stages of NKcell differentiation, since purified CD117high CD94– cells give rise to CD117low/–CD94+ cells. The stromal cell line (EL08.1D2) facilitated the transition from CD117highCD94– to CD117low/–CD94+ via an intermediate phenotype (CD117lowCD94low/–). EL08.1D2 also maintained the mature phenotype, preventing the reversion of CD117low/–CD94+ cells to the intermediate (CD117lowCD94low/–) phenotype. An analogous population of CD56+CD117highCD94– cells was found in cord blood. The identified stages of NK-cell differentiation provide evidence for coordinated acquisition of HLA-specific inhibitory receptors (ie, CD94/NKG2A) and function in developing human NK cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. S. Kaufman Toward clinical therapies using hematopoietic cells derived from human pluripotent stem cells Blood, October 22, 2009; 114(17): 3513 - 3523. [Abstract] [Full Text] [PDF] J. L. Meade, E. B. Wilson, T. D. Holmes, E. A. de Wynter, P. Brett, L. Straszynski, P. A. S. Ballard, J. A. 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