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.
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-gamma-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.
Spaggiari
Grazia Maria
GM
Istituto Giannina Gaslini, Largo Gerolamo Gaslini 5, 16147 Genova, Italy.
Capobianco
Andrea
A
Becchetti
Stelvio
S
Mingari
Maria Cristina
MC
Moretta
Lorenzo
L
D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007223:Infant; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation; D008648:Mesoderm / Q000276:immunology; D013234:Stem Cells / Q000276:immunology*
D016207:Cytokines; D007376:Interleukin-2