PMID- 25950680
OWN - NLM
STAT- MEDLINE
DCOM- 20160413
LR  - 20220316
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 5
DP  - 2015
TI  - 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.
PG  - e0125544
LID - 10.1371/journal.pone.0125544 [doi]
LID - e0125544
AB  - 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 = 1.69 x 10(-39)). Notably, the specific 
      lysis of the individual hiPSC lines by IL-2-activated NK cells was significantly 
      different (P = 1.72 x 10(-6)) and ranged between 46 % and 64 % in 51Cr-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=8.63 x 10(-6)). Killing was partly dependent on the activating NK 
      receptor DNAM-1 (P = 8.22 x 10(-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.
FAU - Kruse, Vanessa
AU  - Kruse V
AD  - Department of Cardiology and Pneumology, University Medical Center Gottingen, 
      Gottingen, Germany.
FAU - Hamann, Carina
AU  - Hamann C
AD  - Department of Cellular and Molecular Immunology, University Medical Center 
      Gottingen, Gottingen, Germany; DZHK (German Center for Cardiovascular Research), 
      Partner site Gottingen, Germany.
FAU - Monecke, Sebastian
AU  - Monecke S
AD  - Department of Cellular and Molecular Immunology, University Medical Center 
      Gottingen, Gottingen, Germany; DZHK (German Center for Cardiovascular Research), 
      Partner site Gottingen, Germany.
FAU - Cyganek, Lukas
AU  - Cyganek L
AD  - Department of Cardiology and Pneumology, University Medical Center Gottingen, 
      Gottingen, Germany; DZHK (German Center for Cardiovascular Research), Partner 
      site Gottingen, Germany.
FAU - Elsner, Leslie
AU  - Elsner L
AD  - Department of Cellular and Molecular Immunology, University Medical Center 
      Gottingen, Gottingen, Germany.
FAU - Hubscher, Daniela
AU  - Hubscher D
AD  - Department of Cardiology and Pneumology, University Medical Center Gottingen, 
      Gottingen, Germany; DZHK (German Center for Cardiovascular Research), Partner 
      site Gottingen, Germany.
FAU - Walter, Lutz
AU  - Walter L
AD  - Primate Genetics Laboratory, German Primate Center, Gottingen, Germany.
FAU - Streckfuss-Bomeke, Katrin
AU  - Streckfuss-Bomeke K
AD  - Department of Cardiology and Pneumology, University Medical Center Gottingen, 
      Gottingen, Germany; DZHK (German Center for Cardiovascular Research), Partner 
      site Gottingen, Germany.
FAU - Guan, Kaomei
AU  - Guan K
AD  - Department of Cardiology and Pneumology, University Medical Center Gottingen, 
      Gottingen, Germany; DZHK (German Center for Cardiovascular Research), Partner 
      site Gottingen, Germany.
FAU - Dressel, Ralf
AU  - Dressel R
AD  - Department of Cellular and Molecular Immunology, University Medical Center 
      Gottingen, Gottingen, Germany; DZHK (German Center for Cardiovascular Research), 
      Partner site Gottingen, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150507
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antigens, Differentiation, T-Lymphocyte)
RN  - 0 (CD226 antigen)
RN  - 0 (Interleukin-2)
SB  - IM
MH  - Antigens, Differentiation, T-Lymphocyte/*physiology
MH  - Cell Line
MH  - Humans
MH  - Induced Pluripotent Stem Cells/*immunology
MH  - Interleukin-2/pharmacology
MH  - Killer Cells, Natural/drug effects/*immunology
PMC - PMC4423859
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/05/08 06:00
MHDA- 2016/04/14 06:00
PMCR- 2015/05/07
CRDT- 2015/05/08 06:00
PHST- 2014/10/21 00:00 [received]
PHST- 2015/03/25 00:00 [accepted]
PHST- 2015/05/08 06:00 [entrez]
PHST- 2015/05/08 06:00 [pubmed]
PHST- 2016/04/14 06:00 [medline]
PHST- 2015/05/07 00:00 [pmc-release]
AID - PONE-D-14-46772 [pii]
AID - 10.1371/journal.pone.0125544 [doi]
PST - epublish
SO  - PLoS One. 2015 May 7;10(5):e0125544. doi: 10.1371/journal.pone.0125544. 
      eCollection 2015.