Abstract
BackgroundThe aim of this paper is to study the function of allogeneic and autologous NK cells against Dental Pulp Stem Cells (DPSCs) and Mesenchymal Stem Cells (MSCs) and to determine the function of NK cells in a three way interaction with monocytes and stem cells.Methodology/Principal FindingsWe demonstrate here that freshly isolated untreated or IL-2 treated NK cells are potent inducers of cell death in DPSCs and MSCs, and that anti-CD16 antibody which induces functional split anergy and apoptosis in NK cells inhibits NK cell mediated lysis of DPSCs and MSCs. Monocytes co-cultured with either DPSCs or MSCs decrease lysis of stem cells by untreated or IL-2 treated NK cells. Monocytes also prevent NK cell apoptosis thereby raising the overall survival and function of NK cells, DPSCs or MSCs. Both total population of monocytes and those depleted of CD16+ subsets were able to prevent NK cell mediated lysis of MSCs and DPSCs, and to trigger an increased secretion of IFN-γ by IL-2 treated NK cells. Protection of stem cells from NK cell mediated lysis was also seen when monocytes were sorted out from stem cells before they were added to NK cells. However, this effect was not specific to monocytes since the addition of T and B cells to stem cells also protected stem cells from NK cell mediated lysis. NK cells were found to lyse monocytes, as well as T and B cells.Conclusion/SignificanceBy increasing the release of IFN-γ and decreasing the cytotoxic function of NK cells monocytes are able to shield stem cells from killing by the NK cells, resulting in an increased protection and differentiation of stem cells. More importantly studies reported in this paper indicate that anti-CD16 antibody can be used to prevent NK cell induced rejection of stem cells.
Highlights
Previous reports demonstrated significant immunomodulatory effect of Mesenchymal Stem Cells (MSCs) on different immune effector subsets such as cytotoxic T cells and Natural Killer (NK) cells [1,2,3,4,5]
In agreement with previous studies we show in this report that NK cells can target and kill MSCs significantly
We demonstrate for the first time that Dental Pulp Stem Cells (DPSCs) are targets of NK cell mediated killing, and that stem cells in general have exquisite sensitivity to NK cell mediated lysis
Summary
Previous reports demonstrated significant immunomodulatory effect of Mesenchymal Stem Cells (MSCs) on different immune effector subsets such as cytotoxic T cells and Natural Killer (NK) cells [1,2,3,4,5]. On one hand the MSCs were shown to be immunosuppressive and on the other they were found to be sensitive to lysis by the NK cells These diverse results prompted us to evaluate the function of NK cells against two different types of stem cells, namely DPSCs and MSCs. some information is known about the function of NK cells against MSCs, no studies have been performed far to determine the effect of NK cells on DPSCs. DPSCs were shown to form colonies in vitro, and they were capable of osteogenic, chondrogenic and adipogenic differentiation [10]. The aim of this paper is to study the function of allogeneic and autologous NK cells against Dental Pulp Stem Cells (DPSCs) and Mesenchymal Stem Cells (MSCs) and to determine the function of NK cells in a three way interaction with monocytes and stem cells
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