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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 13, 2005 Accepted October 5, 2005 Mesenchymal stem cell (MSC)/natural killer (NK) cell interactions: evidence that activated NK cells are capable of killing MSC while MSC can inhibit IL-2-induced NK cell proliferation Grazia Maria Spaggiari, Andrea Capobianco, Stelvio Becchetti, Maria Cristina Mingari, and Lorenzo Moretta* Istituto Giannina Gaslini, Genova, Italy; Universita' degli Studi di Genova, Centro di Eccellenza per la Ricerca Biomedica, Genova, Italy Universita' degli Studi di Genova, Centro di Eccellenza per la Ricerca Biomedica, Genova, Italy; Universita' degli Studi di Genova, Dipartimento di Oncologia, Biologia e Genetica, Genova, Italy Istituto Giannina Gaslini, Genova, Italy Universita' degli Studi di Genova, Dipartimento di Oncologia, Biologia e Genetica, Genova, Italy; Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy Istituto Giannina Gaslini, Genova, Italy; Universita' degli Studi di Genova, Centro di Eccellenza per la Ricerca Biomedica, Genova, Italy; Universita' degli Studi di Genova, Dipartimento di Medicina Sperimentale, Genova, Italy * Corresponding author; email: lorenzomoretta{at}ospedale-gaslini.ge.it. In recent years, MSC have been shown to inhibit T lymphocyte proliferation induced by alloantigens or mitogens. However, no substantial information is available regarding their effect on NK cells. Here we show that MSC sharply inhibit IL-2-induced proliferation of resting NK cells while they only partially affect proliferation of activated NK cells. In addition, we show that IL-2-activated NK cells (but not freshly isolated NK cells) efficiently lyse both autologous and allogeneic MSC. The activating NK receptors NKp30, NKG2D and DNAM-1 represented the major receptors responsible for the induction of NK-mediated cytotoxicity against MSC. Accordingly, MSC expressed the known ligands for these activating NK receptors, ie ULBPs, PVR and Nectin-2. Moreover, NK-mediated lysis was inhibited when IFN--exposed MSC were used as target cells as a consequence of the upregulation of HLA-class I molecules at the MSC cell surface. The interaction between NK cells and MSC resulted not only in lysis of MSC but also in cytokine production by NK cells. These results should be taken into account when evaluating the possible use of MSC in novel therapeutic strategies designed to improve engraftment and/or suppress GvHD in bone marrow transplantation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Ren, X. Zhao, L. Zhang, J. Zhang, A. L'Huillier, W. Ling, A. I. Roberts, A. D. Le, S. Shi, C. Shao, et al. Inflammatory Cytokine-Induced Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1 in Mesenchymal Stem Cells Are Critical for Immunosuppression J. Immunol., March 1, 2010; 184(5): 2321 - 2328. [Abstract] [Full Text] [PDF] M. Aslam, R. Baveja, O. D. Liang, A. Fernandez-Gonzalez, C. Lee, S. A. Mitsialis, and S. 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