Efficient Killing of Murine Pluripotent Stem Cells by Natural Killer (NK) Cells Requires Activation by Cytokines and Partly Depends on the Activating NK Receptor NKG2D
Natural killer (NK) cells play an important role as cytotoxic effector cells, which scan the organism for infected or tumorigenic cells. Conflicting data have been published whether NK cells can also kill allogeneic or even autologous pluripotent stem cells (PSCs) and which receptors are involved. A...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00870/full |
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| author | Carina Gröschel Carina Gröschel Daniela Hübscher Daniela Hübscher Jessica Nolte Sebastian Monecke Sebastian Monecke André Sasse Leslie Elsner Walter Paulus Claudia Trenkwalder Bojan Polić Ahmed Mansouri Ahmed Mansouri Kaomei Guan Kaomei Guan Ralf Dressel Ralf Dressel |
| author_facet | Carina Gröschel Carina Gröschel Daniela Hübscher Daniela Hübscher Jessica Nolte Sebastian Monecke Sebastian Monecke André Sasse Leslie Elsner Walter Paulus Claudia Trenkwalder Bojan Polić Ahmed Mansouri Ahmed Mansouri Kaomei Guan Kaomei Guan Ralf Dressel Ralf Dressel |
| author_sort | Carina Gröschel |
| collection | DOAJ |
| description | Natural killer (NK) cells play an important role as cytotoxic effector cells, which scan the organism for infected or tumorigenic cells. Conflicting data have been published whether NK cells can also kill allogeneic or even autologous pluripotent stem cells (PSCs) and which receptors are involved. A clarification of this question is relevant since an activity of NK cells against PSCs could reduce the risk of teratoma growth after transplantation of PSC-derived grafts. Therefore, the hypothesis has been tested that the activity of NK cells against PSCs depends on cytokine activation and specifically on the activating NK receptor NKG2D. It is shown that a subcutaneous injection of autologous iPSCs failed to activate NK cells against these iPSCs and can give rise to teratomas. In agreement with this result, several PSC lines, including two iPSC, two embryonic stem cell (ESC), and two so-called multipotent adult germline stem cell (maGSC) lines, were largely resistant against resting NK cells although differences in killing were found at low level. All PSC lines were killed by interleukin (IL)-2-activated NK cells, and maGSCs were better killed than the other PSC types. The PSCs expressed ligands of the activating NK receptor NKG2D and NKG2D-deficient NK cells from Klrk1−/− mice were impaired in their cytotoxic activity against PSCs. The low-cytotoxic activity of resting NK cells was almost completely dependent on NKG2D. The cytotoxic activity of IL-2-activated NKG2D-deficient NK cells against PSCs was reduced, indicating that also other activating receptors on cytokine-activated NK cells must be engaged by ligands on PSCs. Thus, NKG2D is an important activating receptor involved in killing of murine PSCs. However, NK cells need to be activated by cytokines before they efficiently target PSCs and then also other NK receptors become relevant. These features of NK cells might be relevant for transplantation of PSC-derived grafts since NK cells have the capability to kill undifferentiated cells, which might be present in grafts in trace amounts. |
| first_indexed | 2024-12-10T12:09:52Z |
| format | Article |
| id | doaj.art-a4190ebf838e4887888c04348b0cf25c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T12:09:52Z |
| publishDate | 2017-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-a4190ebf838e4887888c04348b0cf25c2022-12-22T01:49:24ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-07-01810.3389/fimmu.2017.00870280608Efficient Killing of Murine Pluripotent Stem Cells by Natural Killer (NK) Cells Requires Activation by Cytokines and Partly Depends on the Activating NK Receptor NKG2DCarina Gröschel0Carina Gröschel1Daniela Hübscher2Daniela Hübscher3Jessica Nolte4Sebastian Monecke5Sebastian Monecke6André Sasse7Leslie Elsner8Walter Paulus9Claudia Trenkwalder10Bojan Polić11Ahmed Mansouri12Ahmed Mansouri13Kaomei Guan14Kaomei Guan15Ralf Dressel16Ralf Dressel17Institute of Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, GermanyDZHK (German Center for Cardiovascular Research), Göttingen, GermanyDZHK (German Center for Cardiovascular Research), Göttingen, GermanyDepartment of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, GermanyInstitute of Human Genetics, University Medical Center Göttingen, Göttingen, GermanyInstitute of Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, GermanyDZHK (German Center for Cardiovascular Research), Göttingen, GermanyInstitute of Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, GermanyInstitute of Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, GermanyDepartment of Clinical Neurophysiology, University Medical Center Göttingen, Göttingen, GermanyDepartment of Neurosurgery, University of Göttingen, Göttingen, GermanyDepartment of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, CroatiaDepartment of Clinical Neurophysiology, University Medical Center Göttingen, Göttingen, GermanyDepartment of Molecular Cell Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, GermanyDepartment of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, GermanyInstitute of Pharmacology and Toxicology, Technische Universität Dresden, Dresden, GermanyInstitute of Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, GermanyDZHK (German Center for Cardiovascular Research), Göttingen, GermanyNatural killer (NK) cells play an important role as cytotoxic effector cells, which scan the organism for infected or tumorigenic cells. Conflicting data have been published whether NK cells can also kill allogeneic or even autologous pluripotent stem cells (PSCs) and which receptors are involved. A clarification of this question is relevant since an activity of NK cells against PSCs could reduce the risk of teratoma growth after transplantation of PSC-derived grafts. Therefore, the hypothesis has been tested that the activity of NK cells against PSCs depends on cytokine activation and specifically on the activating NK receptor NKG2D. It is shown that a subcutaneous injection of autologous iPSCs failed to activate NK cells against these iPSCs and can give rise to teratomas. In agreement with this result, several PSC lines, including two iPSC, two embryonic stem cell (ESC), and two so-called multipotent adult germline stem cell (maGSC) lines, were largely resistant against resting NK cells although differences in killing were found at low level. All PSC lines were killed by interleukin (IL)-2-activated NK cells, and maGSCs were better killed than the other PSC types. The PSCs expressed ligands of the activating NK receptor NKG2D and NKG2D-deficient NK cells from Klrk1−/− mice were impaired in their cytotoxic activity against PSCs. The low-cytotoxic activity of resting NK cells was almost completely dependent on NKG2D. The cytotoxic activity of IL-2-activated NKG2D-deficient NK cells against PSCs was reduced, indicating that also other activating receptors on cytokine-activated NK cells must be engaged by ligands on PSCs. Thus, NKG2D is an important activating receptor involved in killing of murine PSCs. However, NK cells need to be activated by cytokines before they efficiently target PSCs and then also other NK receptors become relevant. These features of NK cells might be relevant for transplantation of PSC-derived grafts since NK cells have the capability to kill undifferentiated cells, which might be present in grafts in trace amounts.http://journal.frontiersin.org/article/10.3389/fimmu.2017.00870/fullteratomaautologous transplantationembryonic stem cellsinduced pluripotent stem cellsmultipotent adult germline stem cellsnatural killer cells |
| spellingShingle | Carina Gröschel Carina Gröschel Daniela Hübscher Daniela Hübscher Jessica Nolte Sebastian Monecke Sebastian Monecke André Sasse Leslie Elsner Walter Paulus Claudia Trenkwalder Bojan Polić Ahmed Mansouri Ahmed Mansouri Kaomei Guan Kaomei Guan Ralf Dressel Ralf Dressel Efficient Killing of Murine Pluripotent Stem Cells by Natural Killer (NK) Cells Requires Activation by Cytokines and Partly Depends on the Activating NK Receptor NKG2D Frontiers in Immunology teratoma autologous transplantation embryonic stem cells induced pluripotent stem cells multipotent adult germline stem cells natural killer cells |
| title | Efficient Killing of Murine Pluripotent Stem Cells by Natural Killer (NK) Cells Requires Activation by Cytokines and Partly Depends on the Activating NK Receptor NKG2D |
| title_full | Efficient Killing of Murine Pluripotent Stem Cells by Natural Killer (NK) Cells Requires Activation by Cytokines and Partly Depends on the Activating NK Receptor NKG2D |
| title_fullStr | Efficient Killing of Murine Pluripotent Stem Cells by Natural Killer (NK) Cells Requires Activation by Cytokines and Partly Depends on the Activating NK Receptor NKG2D |
| title_full_unstemmed | Efficient Killing of Murine Pluripotent Stem Cells by Natural Killer (NK) Cells Requires Activation by Cytokines and Partly Depends on the Activating NK Receptor NKG2D |
| title_short | Efficient Killing of Murine Pluripotent Stem Cells by Natural Killer (NK) Cells Requires Activation by Cytokines and Partly Depends on the Activating NK Receptor NKG2D |
| title_sort | efficient killing of murine pluripotent stem cells by natural killer nk cells requires activation by cytokines and partly depends on the activating nk receptor nkg2d |
| topic | teratoma autologous transplantation embryonic stem cells induced pluripotent stem cells multipotent adult germline stem cells natural killer cells |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00870/full |
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