Immunological Properties of Murine Parthenogenetic Stem Cells and Their Differentiation Products
The perspective to transplant grafts derived from pluripotent stem cells has gained much attention in recent years. Parthenogenetic stem cells (PSCs) are an alternative pluripotent stem cell type that is attractive as source of grafts for allogeneic transplantations because most PSCs are haploidenti...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2017-08-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00924/full |
| _version_ | 1811241332632453120 |
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| author | Hannah Johannsen Vijayakumar Muppala Carina Gröschel Carina Gröschel Sebastian Monecke Sebastian Monecke Leslie Elsner Michael Didié Michael Didié Wolfram-Hubertus Zimmermann Wolfram-Hubertus Zimmermann Ralf Dressel Ralf Dressel |
| author_facet | Hannah Johannsen Vijayakumar Muppala Carina Gröschel Carina Gröschel Sebastian Monecke Sebastian Monecke Leslie Elsner Michael Didié Michael Didié Wolfram-Hubertus Zimmermann Wolfram-Hubertus Zimmermann Ralf Dressel Ralf Dressel |
| author_sort | Hannah Johannsen |
| collection | DOAJ |
| description | The perspective to transplant grafts derived from pluripotent stem cells has gained much attention in recent years. Parthenogenetic stem cells (PSCs) are an alternative pluripotent stem cell type that is attractive as source of grafts for allogeneic transplantations because most PSCs are haploidentical for the major histocompatibility complex (MHC). This reduced immunogenetic complexity of PSCs could tremendously simplify the search for MHC-matched allogeneic stem cells. In this study, we have characterized immunological properties of the MHC haploidentical PSC line A3 (H2d/d) and the heterologous PSC line A6 (H2b/d). Both PSC lines largely lack MHC class I molecules, which present peptides to cytotoxic T lymphocytes (CTLs) and serve as ligands for inhibitory natural killer (NK) receptors. They express ligands for activating NK receptors, including the NKG2D ligand RAE-1, and the DNAM-1 ligands CD112 and CD155. Consequently, both PSC lines are highly susceptible to killing by IL-2-activated NK cells. In vitro-differentiated cells acquire resistance and downregulate ligands for activating NK receptors but fail to upregulate MHC class I molecules. The PSC line A6 and differentiated A6 cells are largely resistant to CTLs derived from T cell receptor transgenic OT-I mice after pulsing of the targets with the appropriate peptide. The high susceptibility to killing by activated NK cells may constitute a general feature of pluripotent stem cells as it has been also found with other pluripotent stem cell types. This activity potentially increases the safety of transplantations, if grafts contain traces of undifferentiated cells that could be tumorigenic in the recipient. |
| first_indexed | 2024-04-12T13:34:45Z |
| format | Article |
| id | doaj.art-87a11bfa7c544e21816e2fdee3ed3a3c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T13:34:45Z |
| publishDate | 2017-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-87a11bfa7c544e21816e2fdee3ed3a3c2022-12-22T03:31:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-08-01810.3389/fimmu.2017.00924270439Immunological Properties of Murine Parthenogenetic Stem Cells and Their Differentiation ProductsHannah Johannsen0Vijayakumar Muppala1Carina Gröschel2Carina Gröschel3Sebastian Monecke4Sebastian Monecke5Leslie Elsner6Michael Didié7Michael Didié8Wolfram-Hubertus Zimmermann9Wolfram-Hubertus Zimmermann10Ralf Dressel11Ralf Dressel12Institute of Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, GermanyInstitute of Pharmacology and Toxicology, University Medical Center Göttingen, Göttingen, GermanyInstitute of Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, GermanyDZHK (German Center for Cardiovascular Research), Partner Site Göttingen, Göttingen, GermanyInstitute of Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, GermanyDZHK (German Center for Cardiovascular Research), Partner Site Göttingen, Göttingen, GermanyInstitute of Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, GermanyInstitute of Pharmacology and Toxicology, University Medical Center Göttingen, Göttingen, GermanyDZHK (German Center for Cardiovascular Research), Partner Site Göttingen, Göttingen, GermanyInstitute of Pharmacology and Toxicology, University Medical Center Göttingen, Göttingen, GermanyDZHK (German Center for Cardiovascular Research), Partner Site Göttingen, Göttingen, GermanyInstitute of Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, GermanyDZHK (German Center for Cardiovascular Research), Partner Site Göttingen, Göttingen, GermanyThe perspective to transplant grafts derived from pluripotent stem cells has gained much attention in recent years. Parthenogenetic stem cells (PSCs) are an alternative pluripotent stem cell type that is attractive as source of grafts for allogeneic transplantations because most PSCs are haploidentical for the major histocompatibility complex (MHC). This reduced immunogenetic complexity of PSCs could tremendously simplify the search for MHC-matched allogeneic stem cells. In this study, we have characterized immunological properties of the MHC haploidentical PSC line A3 (H2d/d) and the heterologous PSC line A6 (H2b/d). Both PSC lines largely lack MHC class I molecules, which present peptides to cytotoxic T lymphocytes (CTLs) and serve as ligands for inhibitory natural killer (NK) receptors. They express ligands for activating NK receptors, including the NKG2D ligand RAE-1, and the DNAM-1 ligands CD112 and CD155. Consequently, both PSC lines are highly susceptible to killing by IL-2-activated NK cells. In vitro-differentiated cells acquire resistance and downregulate ligands for activating NK receptors but fail to upregulate MHC class I molecules. The PSC line A6 and differentiated A6 cells are largely resistant to CTLs derived from T cell receptor transgenic OT-I mice after pulsing of the targets with the appropriate peptide. The high susceptibility to killing by activated NK cells may constitute a general feature of pluripotent stem cells as it has been also found with other pluripotent stem cell types. This activity potentially increases the safety of transplantations, if grafts contain traces of undifferentiated cells that could be tumorigenic in the recipient.http://journal.frontiersin.org/article/10.3389/fimmu.2017.00924/fullpluripotent stem cellsnatural killer cellscytotoxic T lymphocytesmajor histocompatibility complex class I moleculesnatural killer receptor ligandsstem cell differentiation |
| spellingShingle | Hannah Johannsen Vijayakumar Muppala Carina Gröschel Carina Gröschel Sebastian Monecke Sebastian Monecke Leslie Elsner Michael Didié Michael Didié Wolfram-Hubertus Zimmermann Wolfram-Hubertus Zimmermann Ralf Dressel Ralf Dressel Immunological Properties of Murine Parthenogenetic Stem Cells and Their Differentiation Products Frontiers in Immunology pluripotent stem cells natural killer cells cytotoxic T lymphocytes major histocompatibility complex class I molecules natural killer receptor ligands stem cell differentiation |
| title | Immunological Properties of Murine Parthenogenetic Stem Cells and Their Differentiation Products |
| title_full | Immunological Properties of Murine Parthenogenetic Stem Cells and Their Differentiation Products |
| title_fullStr | Immunological Properties of Murine Parthenogenetic Stem Cells and Their Differentiation Products |
| title_full_unstemmed | Immunological Properties of Murine Parthenogenetic Stem Cells and Their Differentiation Products |
| title_short | Immunological Properties of Murine Parthenogenetic Stem Cells and Their Differentiation Products |
| title_sort | immunological properties of murine parthenogenetic stem cells and their differentiation products |
| topic | pluripotent stem cells natural killer cells cytotoxic T lymphocytes major histocompatibility complex class I molecules natural killer receptor ligands stem cell differentiation |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00924/full |
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