Expression of human cytokines dramatically improves reconstitution of specific human-blood lineage cells in humanized mice
Adoptive transfer of human hematopoietic stem cells (HSCs) into mice lacking T, B and natural killer (NK) cells leads to development of human-blood lineage cells in the recipient mice (humanized mice). Although human B cell reconstitution is robust and T cell reconstitution is reasonable in the reci...
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences
2011
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| Online Access: | http://hdl.handle.net/1721.1/60888 https://orcid.org/0000-0002-5687-6154 |
| _version_ | 1826193199880732672 |
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| author | Chen, Qingfeng Khoury, Maroun Chen, Jianzhu |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Chen, Qingfeng Khoury, Maroun Chen, Jianzhu |
| author_sort | Chen, Qingfeng |
| collection | MIT |
| description | Adoptive transfer of human hematopoietic stem cells (HSCs) into mice lacking T, B and natural killer (NK) cells leads to development of human-blood lineage cells in the recipient mice (humanized mice). Although human B cell reconstitution is robust and T cell reconstitution is reasonable in the recipient mice, reconstitution of NK cells and myeloid cells is generally poor or undetectable. Here, we show that the poor reconstitution is mainly the result of a deficiency of appropriate human cytokines that are necessary for the development and maintenance of these cell lineages. When plasmid DNA encoding human IL-15 and Flt-3/Flk-2 ligand were delivered into humanized mice by hydrodynamic tail-vein injection, the expression of the human cytokine lasted for 2 to 3 weeks and elevated levels of NK cells were induced for more than a month. The cytokine-induced NK cells expressed both activation and inhibitory receptors, killed target cells in vitro, and responded robustly to a virus infection in vivo. Similarly, expression of human GM-CSF and IL-4, macrophage colony stimulating factor, or erythropoietin and IL-3 resulted in significantly enhanced reconstitution of dendritic cells, monocytes/macrophages, or erythrocytes, respectively. Thus, human cytokine gene expression by hydrodynamic delivery is a simple and efficient method to improve reconstitution of specific human-blood cell lineages in humanized mice, providing an important tool for studying human immune responses and disease progression in a small animal model. |
| first_indexed | 2024-09-23T09:35:13Z |
| format | Article |
| id | mit-1721.1/60888 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:35:13Z |
| publishDate | 2011 |
| publisher | National Academy of Sciences |
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| spelling | mit-1721.1/608882022-09-26T12:27:37Z Expression of human cytokines dramatically improves reconstitution of specific human-blood lineage cells in humanized mice Chen, Qingfeng Khoury, Maroun Chen, Jianzhu Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Chen, Jianzhu Khoury, Maroun Chen, Jianzhu Adoptive transfer of human hematopoietic stem cells (HSCs) into mice lacking T, B and natural killer (NK) cells leads to development of human-blood lineage cells in the recipient mice (humanized mice). Although human B cell reconstitution is robust and T cell reconstitution is reasonable in the recipient mice, reconstitution of NK cells and myeloid cells is generally poor or undetectable. Here, we show that the poor reconstitution is mainly the result of a deficiency of appropriate human cytokines that are necessary for the development and maintenance of these cell lineages. When plasmid DNA encoding human IL-15 and Flt-3/Flk-2 ligand were delivered into humanized mice by hydrodynamic tail-vein injection, the expression of the human cytokine lasted for 2 to 3 weeks and elevated levels of NK cells were induced for more than a month. The cytokine-induced NK cells expressed both activation and inhibitory receptors, killed target cells in vitro, and responded robustly to a virus infection in vivo. Similarly, expression of human GM-CSF and IL-4, macrophage colony stimulating factor, or erythropoietin and IL-3 resulted in significantly enhanced reconstitution of dendritic cells, monocytes/macrophages, or erythrocytes, respectively. Thus, human cytokine gene expression by hydrodynamic delivery is a simple and efficient method to improve reconstitution of specific human-blood cell lineages in humanized mice, providing an important tool for studying human immune responses and disease progression in a small animal model. National Institutes of Health (U.S) (Grant AI69208) MIT-Singapore Alliance 2011-02-04T12:47:08Z 2011-02-04T12:47:08Z 2009-12 2009-09 Article http://purl.org/eprint/type/JournalArticle http://hdl.handle.net/1721.1/60888 Chen, Qingfeng, Maroun Khoury, and Jianzhu Chen. “Expression of human cytokines dramatically improves reconstitution of specific human-blood lineage cells in humanized mice.” Proceedings of the National Academy of Sciences 106.51 (2009): 21783 -21788. Copyright ©2009 by the National Academy of Sciences 19966223 https://orcid.org/0000-0002-5687-6154 en_US http://dx.doi.org/10.1073/pnas.0912274106 Proceedings of the National Academy of Sciences of the United States of America Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences PNAS |
| spellingShingle | Chen, Qingfeng Khoury, Maroun Chen, Jianzhu Expression of human cytokines dramatically improves reconstitution of specific human-blood lineage cells in humanized mice |
| title | Expression of human cytokines dramatically improves reconstitution of specific human-blood lineage cells in humanized mice |
| title_full | Expression of human cytokines dramatically improves reconstitution of specific human-blood lineage cells in humanized mice |
| title_fullStr | Expression of human cytokines dramatically improves reconstitution of specific human-blood lineage cells in humanized mice |
| title_full_unstemmed | Expression of human cytokines dramatically improves reconstitution of specific human-blood lineage cells in humanized mice |
| title_short | Expression of human cytokines dramatically improves reconstitution of specific human-blood lineage cells in humanized mice |
| title_sort | expression of human cytokines dramatically improves reconstitution of specific human blood lineage cells in humanized mice |
| url | http://hdl.handle.net/1721.1/60888 https://orcid.org/0000-0002-5687-6154 |
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