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Blood, 15 February 2006, Vol. 107, No. 4, pp. 1484-1490. Prepublished online as a Blood First Edition Paper on October 20, 2005; DOI 10.1182/blood-2005-07-2775. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-07-2775v1 107/4/1484    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 Spaggiari, G. M. Articles by Moretta, L. Search for Related Content PubMed PubMed Citation Articles by Spaggiari, G. M. Articles by Moretta, L. Related Collections Immunobiology Transplantation Stem Cells in Hematology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Mesenchymal stem cell-natural killer cell interactions: evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2-induced NK-cell proliferation Grazia Maria Spaggiari, Andrea Capobianco, Stelvio Becchetti, Maria Cristina Mingari, and Lorenzo Moretta From the Istituto Giannina Gaslini, Genoa; Centro di Eccellenza per la Ricerca Biomedica and Dipartimento di Oncologia, Biologia e Genetica, Università di Genova, Genoa; Istituto Nazionale per la Ricerca sul Cancro, Genoa; and Dipartimento di Medicina Sperimentale, Università di Genova, Genoa, Italy. In recent years, mesenchymal stem cells (MSCs) have been shown to inhibit T-lymphocyte proliferation induced by alloantigens or mitogens. However, no substantial information is available regarding their effect on natural killer (NK) cells. Here we show that MSCs sharply inhibit IL-2-induced proliferation of resting NK cells, whereas they only partially affect the proliferation of activated NK cells. In addition, we show that IL-2-activated NK cells (but not freshly isolated NK cells) efficiently lyse autologous and allogeneic MSCs. The activating NK receptors NKp30, NKG2D, and DNAM-1 represented the major receptors responsible for the induction of NK-mediated cytotoxicity against MSCs. Accordingly, MSCs expressed the known ligands for these activating NK receptors—ULBPs, PVR, and Nectin-2. Moreover, NK-mediated lysis was inhibited when IFN--exposed MSCs were used as target cells as a consequence of the up-regulation of HLA class I molecules at the MSC surface. The interaction between NK cells and MSCs resulted not only in the lysis of MSCs but also in cytokine production by NK cells. These results should be taken into account when evaluating the possible use of MSCs in novel therapeutic strategies designed to improve engraftment or to suppress graft-versus-host disease (GVHD) in bone marrow transplantation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Atoui, D. Shum-Tim, and R. C.J. Chiu Myocardial regenerative therapy: immunologic basis for the potential "universal donor cells". Ann. Thorac. Surg., July 1, 2008; 86(1): 327 - 334. [Abstract] [Full Text] [PDF] G. Lazennec and C. Jorgensen Concise Review: Adult Multipotent Stromal Cells and Cancer: Risk or Benefit? Stem Cells, June 1, 2008; 26(6): 1387 - 1394. [Abstract] [Full Text] [PDF] F. Morandi, L. Raffaghello, G. Bianchi, F. Meloni, A. Salis, E. Millo, S. Ferrone, V. Barnaba, and V. 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