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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.
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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.
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