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Blood, 15 July 2007, Vol. 110, No. 2, pp. 578-586. Prepublished online as a Blood First Edition Paper on March 28, 2007; DOI 10.1182/blood-2006-07-036228. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-07-036228v1 110/2/578    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 Cooley, S. Articles by Miller, J. S. Search for Related Content PubMed PubMed Citation Articles by Cooley, S. Articles by Miller, J. S. Related Collections Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY A subpopulation of human peripheral blood NK cells that lacks inhibitory receptors for self-MHC is developmentally immature Sarah Cooley1, Feng Xiao1, Michelle Pitt1, Michelle Gleason1, Valarie McCullar1, Tracy L. Bergemann2, Karina L. McQueen3, Lisbeth A. Guethlein3, Peter Parham3, and Jeffrey S. Miller1 1 Division of Hematology, Oncology and Transplantation, University of Minnesota Cancer Center, Minneapolis; 2 Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis; 3 Department of Structural Biology, Sherman Fairchild Building, Stanford University School of Medicine, Stanford, CA How receptor acquisition correlates with the functional maturation of natural killer (NK) cells is poorly understood. We used quantitative real-time polymerase chain reaction (PCR) assays to compare NKG2 and killer immunoglobulin-like receptor (KIR) gene expression in NK cells from allogeneic transplant recipients and their donors. Marked differences were observed in the NK subsets of recipients who had 8-fold more CD56bright cells, diminished KIR expression (except 2DL4), and increased NKG2A. In normal blood not all CD56dim cells express KIR, and a novel subpopulation of cells committed to the NK-cell lineage was defined. These cells, which comprise 19.4% ± 2.8% of the CD56dim NK population in healthy donors, express the activating NKG2D and NKG2E receptors but no KIR or NKG2A. Although the CD56dim NKG2A– KIR– NK cells lack "at least one" inhibitory receptor for autologous MHC class I, they are not fully responsive, but rather functionally immature cells with poor cytotoxicity and IFN- production. Upon culture with IL-15 and a stromal cell line, CD56dim and CD56bright KIR– NK cells proliferate, express KIR, and develop cytotoxicity and cytokine-producing potential. These findings have implications for the function of NK cells reconstituting after transplantation and support a model for in vivo development in which CD56bright cells precede CD56dim cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. S. Miller How killers kill Blood, July 15, 2008; 112(2): 213 - 213. [Full Text] [PDF] A. M. Sharkey, L. Gardner, S. Hiby, L. Farrell, R. Apps, L. Masters, J. Goodridge, L. Lathbury, C. A. Stewart, S. Verma, et al. Killer Ig-Like Receptor Expression in Uterine NK Cells Is Biased toward Recognition of HLA-C and Alters with Gestational Age J. Immunol., July 1, 2008; 181(1): 39 - 46. [Abstract] [Full Text] [PDF] A. W. MacFarlane IV, T. Yamazaki, M. Fang, L. J. Sigal, T. Kurosaki, and K. S. 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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] S. Santourlidis, N. Graffmann, J. Christ, and M. Uhrberg Lineage-Specific Transition of Histone Signatures in the Killer Cell Ig-Like Receptor Locus from Hematopoietic Progenitor to NK Cells J. Immunol., January 1, 2008; 180(1): 418 - 425. [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]

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