TY - JOUR
T1 - Mesenchymal stem cell-natural killer cell interactions
T2 - Evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2-induced NK-cell proliferation
AU - Spaggiari, Grazia Maria
AU - Capobianco, Andrea
AU - Becchetti, Stelvio
AU - Mingari, Maria Cristina
AU - Moretta, Lorenzo
PY - 2006/2/15
Y1 - 2006/2/15
N2 - 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-γ-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.
AB - 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-γ-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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U2 - 10.1182/blood-2005-07-2775
DO - 10.1182/blood-2005-07-2775
M3 - Article
C2 - 16239427
AN - SCOPUS:32644438233
VL - 107
SP - 1484
EP - 1490
JO - Blood
JF - Blood
SN - 0006-4971
IS - 4
ER -