Strategies to rescue mesenchymal stem cells (MSCs) and dental pulp stem cells (DPSCs) from NK cell mediated cytotoxicity.
BACKGROUND
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.


RESULTS
We 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-gamma 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.


CONCLUSIONS
By increasing the release of IFN-gamma 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.
Jewett
Anahid
A
Division of Oral Biology and Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry and Medicine, University of California Los Angeles, Los Angeles, California, United States of America. ajewett@ucla.edu
Arasteh
Aida
A
Tseng
Han-Ching
HC
Behel
Armin
A
Arasteh
Hobie
H
Yang
Wendy
W
Cacalano
Nicholas A
NA
Paranjpe
Avina
A
D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003782:Dental Pulp / Q000166:cytology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009000:Monocytes / Q000166:cytology; D017452:Receptors, IgG / Q000096:biosynthesis; D013234:Stem Cells / Q000166:cytology*; D013601:T-Lymphocytes / Q000378:metabolism
D016207:Cytokines; D007376:Interleukin-2; D017452:Receptors, IgG; D007371:Interferon-gamma