HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chan, A. Articles by Bowness, P. Search for Related Content PubMed PubMed Citation Articles by Chan, A. Articles by Bowness, P.

CD56^bright Human NK Cells Differentiate into CD56^dim Cells: Role of Contact with Peripheral Fibroblasts

Antoni Chan^1,*, Deng-Li Hong, Ann Atzberger, Simon Kollnberger^*, Andrew D. Filer, Christopher D. Buckley, Andrew McMichael^*, Tariq Enver and Paul Bowness^*

^* Medical Research Council Human Immunology Unit, and Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom; and Division of Immunity and Infection, Medical Research Council, Centre for Immune Regulation, University of Birmingham, Birmingham, United Kingdom

Human NK cells are divided into CD56^brightCD16^– cells and CD56^dimCD16⁺ cells. We tested the hypothesis that CD56^bright NK cells can differentiate into CD56^dim cells by prospectively isolating and culturing each NK subset in vitro and in vivo. Our results show that CD56^bright cells can differentiate into CD56^dim both in vitro, in the presence of synovial fibroblasts, and in vivo, upon transfer into NOD-SCID mice. In vitro, this differentiation was inhibited by fibroblast growth factor receptor-1 Ab, demonstrating a role of the CD56 and fibroblast growth factor receptor-1 interaction in this process. Differentiated CD56^dim cells had reduced IFN- production but increased perforin expression and cytolysis of cell line K562 targets. Flow cytometric fluorescent in situ hybridization demonstrated that CD56^bright NK cells had longer telomere length compared with CD56^dim NK cells, implying the former are less mature. Our data support a linear differentiation model of human NK development in which immature CD56^bright NK cells can differentiate into CD56^dim cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Address correspondence and reprint requests to Dr. Antoni Chan, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, U.K. E-mail address: achan{at}hammer.imm.ox.ac.uk

² Abbreviations used in this paper: NCAM, neural cell adhesion molecule; FGFR, fibroblast growth factor receptor; PNA, peptide nucleic acid; KIR, killer Ig-related receptor; FLS, fibroblast-like synoviocyte; CD62L, CD62 ligand.

This article has been cited by other articles:

				V. D. Gonzalez, K. Falconer, N. K. Bjorkstrom, K. G. Blom, O. Weiland, H.-G. Ljunggren, A. Alaeus, and J. K. Sandberg Expansion of Functionally Skewed CD56-Negative NK Cells in Chronic Hepatitis C Virus Infection: Correlation with Outcome of Pegylated IFN-{alpha} and Ribavirin Treatment J. Immunol., November 15, 2009; 183(10): 6612 - 6618. [Abstract] [Full Text] [PDF]

				S. WULFF, R. PRIES, K. BORNGEN, T. TRENKLE, and B. WOLLENBERG Decreased Levels of Circulating Regulatory NK Cells in Patients with Head and Neck Cancer throughout all Tumor Stages Anticancer Res, August 1, 2009; 29(8): 3053 - 3057. [Abstract] [Full Text] [PDF]

				N. D. Huntington, N. Legrand, N. L. Alves, B. Jaron, K. Weijer, A. Plet, E. Corcuff, E. Mortier, Y. Jacques, H. Spits, et al. IL-15 trans-presentation promotes human NK cell development and differentiation in vivo J. Exp. Med., January 16, 2009; 206(1): 25 - 34. [Abstract] [Full Text] [PDF]

				N. Dulphy, P. Haas, M. Busson, S. Belhadj, R. Peffault de Latour, M. Robin, M. Carmagnat, P. Loiseau, R. Tamouza, C. Scieux, et al. An Unusual CD56brightCD16low NK Cell Subset Dominates the Early Posttransplant Period following HLA-Matched Hematopoietic Stem Cell Transplantation J. Immunol., August 1, 2008; 181(3): 2227 - 2237. [Abstract] [Full Text] [PDF]

				L Golden-Mason, L Madrigal-Estebas, E McGrath, M J Conroy, E J Ryan, J E Hegarty, C O'Farrelly, and D G Doherty Altered natural killer cell subset distributions in resolved and persistent hepatitis C virus infection following single source exposure Gut, August 1, 2008; 57(8): 1121 - 1128. [Abstract] [Full Text] [PDF]

				M. A. Caligiuri Human natural killer cells Blood, August 1, 2008; 112(3): 461 - 469. [Abstract] [Full Text] [PDF]

				T. Strowig, F. Brilot, and C. Munz Noncytotoxic Functions of NK Cells: Direct Pathogen Restriction and Assistance to Adaptive Immunity J. Immunol., June 15, 2008; 180(12): 7785 - 7791. [Abstract] [Full Text] [PDF]

				E. Ullrich, M. Bonmort, G. Mignot, B. Jacobs, D. Bosisio, S. Sozzani, A. Jalil, F. Louache, E. Bulanova, F. Geissman, et al. Trans-Presentation of IL-15 Dictates IFN-Producing Killer Dendritic Cells Effector Functions J. Immunol., June 15, 2008; 180(12): 7887 - 7897. [Abstract] [Full Text] [PDF]

				M. T. M. Vossen, M. Matmati, K. M. L. Hertoghs, P. A. Baars, M.-R. Gent, G. Leclercq, J. Hamann, T. W. Kuijpers, and R. A. W. van Lier CD27 Defines Phenotypically and Functionally Different Human NK Cell Subsets J. Immunol., March 15, 2008; 180(6): 3739 - 3745. [Abstract] [Full Text] [PDF]

				M. De Smedt, T. Taghon, I. Van de Walle, G. De Smet, G. Leclercq, and J. Plum Notch signaling induces cytoplasmic CD3{epsilon} expression in human differentiating NK cells Blood, October 1, 2007; 110(7): 2696 - 2703. [Abstract] [Full Text] [PDF]