Human Induced Pluripotent Stem Cells Are Targets for Allogeneic and Autologous Natural Killer (NK) Cells and Killing Is Partly Mediated by the Activating NK Receptor DNAM-1

2015 | journal article; research paper. A publication with affiliation to the University of Göttingen.

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​Human Induced Pluripotent Stem Cells Are Targets for Allogeneic and Autologous Natural Killer (NK) Cells and Killing Is Partly Mediated by the Activating NK Receptor DNAM-1​
Kruse, V.; Hamann, C.; Monecke, S.; Cyganek, L. ; Elsner, L.; Huebscher, D. & Walter, L. et al.​ (2015) 
PLoS One10(5) art. e0125544​.​ DOI: https://doi.org/10.1371/journal.pone.0125544 

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Authors
Kruse, Vanessa; Hamann, Carina; Monecke, Sebastian; Cyganek, Lukas ; Elsner, Leslie; Huebscher, Daniela; Walter, Lutz; Streckfuss-Boemeke, Katrin ; Guan, Kaomei ; Dressel, Ralf 
Abstract
Human induced pluripotent stem cells (hiPSCs) could be used to generate autologous cells for therapeutic purposes, which are expected to be tolerated by the recipient. However, iPSC-derived grafts are at risk of giving rise to teratomas in the host, if residuals of tumorigenic cells are not rejected by the recipient. We have analyzed the susceptibility of hiPSC lines to allogeneic and autologous natural killer (NK) cells. IL-2-activated, in contrast to resting NK cells killed hiPSC lines efficiently (P= 1.69x10(-39)). Notably, the specific lysis of the individual hiPSC lines by IL-2-activated NK cells was significantly different (P= 1.72x10(-6)) and ranged between 46% and 64% in Cr-51-release assays when compared to K562 cells. The hiPSC lines were killed by both allogeneic and autologous NK cells although autologous NK cells were less efficient (P= 8.63x10(-6)). Killing was partly dependent on the activating NK receptor DNAM-1 (P= 8.22x10(-7)). The DNAM-1 ligands CD112 and CD155 as well as the NKG2D ligands MICA and MICB were expressed on the hiPSC lines. Low amounts of human leukocyte antigen (HLA) class I proteins, which serve as ligands for inhibitory and activating NK receptors were also detected. Thus, the susceptibility to NK cell killing appears to constitute a common feature of hiPSCs. Therefore, NK cells might reduce the risk of teratoma formation even after autologous transplantations of pluripotent stem cell-derived grafts that contain traces of pluripotent cells.
Issue Date
2015
Journal
PLoS One 
Project
SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz 
SFB 1002 | A04: Patienten-spezifische induzierte pluripotente Stammzellen zur funktionellen Untersuchung von Ryanodinrezeptor-Mutationen 
SFB 1002 | C05: Bedeutung von zellulären Immunreaktionen für das kardiale Remodeling und die Therapie der Herzinsuffizienz durch Stammzelltransplantation 
Working Group
RG Cyganek (Stem Cell Unit) 
RG Dressel 
RG Guan (Application of patient-specific induced pluripotent stem cells in disease modelling) 
ISSN
1932-6203
Sponsor
Open-Access Publikationsfonds 2015

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