Predominant development of mature and functional human NK cells in a novel human IL-2-producing transgenic NOG mouse
We generated a severe immunodeficient NOD/Shi-scid-IL-2Rγ(null) (NOG) mouse substrain expressing the transgenic human IL-2 gene (NOG-IL-2 Tg). Upon transfer of human cord blood-derived hematopoietic stem cells (HSCs), CD3(-)CD56(high)CD16(+/-) cells developed unexpectedly, predominantly in the NOG-I...
Gespeichert in:
| Veröffentlicht in: | The Journal of immunology (1950) 2015-04, Vol.194 (7), p.3513-3525 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 3525 |
|---|---|
| container_issue | 7 |
| container_start_page | 3513 |
| container_title | The Journal of immunology (1950) |
| container_volume | 194 |
| creator | Katano, Ikumi Takahashi, Takeshi Ito, Ryoji Kamisako, Tsutomu Mizusawa, Takuma Ka, Yuyo Ogura, Tomoyuki Suemizu, Hiroshi Kawakami, Yutaka Ito, Mamoru |
| description | We generated a severe immunodeficient NOD/Shi-scid-IL-2Rγ(null) (NOG) mouse substrain expressing the transgenic human IL-2 gene (NOG-IL-2 Tg). Upon transfer of human cord blood-derived hematopoietic stem cells (HSCs), CD3(-)CD56(high)CD16(+/-) cells developed unexpectedly, predominantly in the NOG-IL-2 Tg (hu-HSC NOG-IL-2 Tg). These cells expressed various NK receptors, including NKp30, NKp44, NKp46, NKG2D, and CD94, as well as a diverse set of killer cell Ig-like receptor molecules at levels comparable to normal human NK cells from the peripheral blood, which is evidence of their maturity. They produced levels of granzyme A as high as in human peripheral blood-derived NK cells, and a considerable amount of perforin protein was detected in the plasma. Human NK cells in hu-HSC NOG-IL-2 Tg produced IFN-γ upon stimulation, and IL-2, IL-15, or IL-12 treatment augmented the in vitro cytotoxicity. Inoculation of K562 leukemia cells into hu-HSC NOG-IL-2 Tg caused complete rejection of the tumor cells, whereas inoculation into hu-HSC NOG fully reconstituted with human B, T, and some NK cells did not. Moreover, when a CCR4(+) Hodgkin's lymphoma cell line was inoculated s.c. into hu-HSC NOG-IL-2 Tg, the tumor growth was significantly suppressed by treatment with a therapeutic humanized anti-CCR4 Ab (mogamulizumab), suggesting that the human NK cells in the mice exerted active Ab-dependent cellular cytotoxicity in vivo. Taken together, these data suggest that the new NOG-IL-2 Tg strain is a unique model that can be used to investigate the biological and pathological functions of human NK cells in vivo. |
| doi_str_mv | 10.4049/jimmunol.1401323 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1808724002</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1808724002</sourcerecordid><originalsourceid>FETCH-LOGICAL-c440t-2aa56e53aafc3a18aaf9abf247ead4525cf4173dcb0dc8a3af674ae11634bc043</originalsourceid><addsrcrecordid>eNqFkc1PwkAQxTdGI4jePZk9einOfhaOhigSCXjQczPdbrGku4vd1sT_3hLAq6eZZN57eZkfIbcMxhLk9GFbOdf5UI-ZBCa4OCNDphQkWoM-J0MAzhOW6nRArmLcAoAGLi_JgKuUcc7UkLRvjS2Cqzz6lhb229Zh52y_h5I6bLvGUvQFLTtv2ip4rOln59DT1Ss1tq4jrTxF6kNvPF4Wy4QnuyYUnan8hrYN-rixvjJ0tZ5TF7por8lFiXW0N8c5Ih_PT--zl2S5ni9mj8vESAltwhGVtkoglkYgm_RzinnJZWqxkIorU0qWisLkUJgJCix1KtEypoXMDUgxIveH3L7OV2djm7kq7mujt32PjE1gknLZv-l_qdZKTjWkupfCQWqaEGNjy2zXVA6bn4xBtseSnbBkRyy95e6Y3uXOFn-GEwfxC71Mi9U</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1665496076</pqid></control><display><type>article</type><title>Predominant development of mature and functional human NK cells in a novel human IL-2-producing transgenic NOG mouse</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><source>EZB Electronic Journals Library</source><creator>Katano, Ikumi ; Takahashi, Takeshi ; Ito, Ryoji ; Kamisako, Tsutomu ; Mizusawa, Takuma ; Ka, Yuyo ; Ogura, Tomoyuki ; Suemizu, Hiroshi ; Kawakami, Yutaka ; Ito, Mamoru</creator><creatorcontrib>Katano, Ikumi ; Takahashi, Takeshi ; Ito, Ryoji ; Kamisako, Tsutomu ; Mizusawa, Takuma ; Ka, Yuyo ; Ogura, Tomoyuki ; Suemizu, Hiroshi ; Kawakami, Yutaka ; Ito, Mamoru</creatorcontrib><description>We generated a severe immunodeficient NOD/Shi-scid-IL-2Rγ(null) (NOG) mouse substrain expressing the transgenic human IL-2 gene (NOG-IL-2 Tg). Upon transfer of human cord blood-derived hematopoietic stem cells (HSCs), CD3(-)CD56(high)CD16(+/-) cells developed unexpectedly, predominantly in the NOG-IL-2 Tg (hu-HSC NOG-IL-2 Tg). These cells expressed various NK receptors, including NKp30, NKp44, NKp46, NKG2D, and CD94, as well as a diverse set of killer cell Ig-like receptor molecules at levels comparable to normal human NK cells from the peripheral blood, which is evidence of their maturity. They produced levels of granzyme A as high as in human peripheral blood-derived NK cells, and a considerable amount of perforin protein was detected in the plasma. Human NK cells in hu-HSC NOG-IL-2 Tg produced IFN-γ upon stimulation, and IL-2, IL-15, or IL-12 treatment augmented the in vitro cytotoxicity. Inoculation of K562 leukemia cells into hu-HSC NOG-IL-2 Tg caused complete rejection of the tumor cells, whereas inoculation into hu-HSC NOG fully reconstituted with human B, T, and some NK cells did not. Moreover, when a CCR4(+) Hodgkin's lymphoma cell line was inoculated s.c. into hu-HSC NOG-IL-2 Tg, the tumor growth was significantly suppressed by treatment with a therapeutic humanized anti-CCR4 Ab (mogamulizumab), suggesting that the human NK cells in the mice exerted active Ab-dependent cellular cytotoxicity in vivo. Taken together, these data suggest that the new NOG-IL-2 Tg strain is a unique model that can be used to investigate the biological and pathological functions of human NK cells in vivo.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.1401323</identifier><identifier>PMID: 25712215</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Antibody-Dependent Cell Cytotoxicity ; Antigens, Surface - metabolism ; Cell Differentiation ; Cytotoxicity, Immunologic ; Disease Models, Animal ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells - cytology ; Hematopoietic Stem Cells - metabolism ; Humans ; Immunophenotyping ; Interleukin-2 - biosynthesis ; Interleukin-2 - genetics ; Killer Cells, Natural - cytology ; Killer Cells, Natural - immunology ; Killer Cells, Natural - metabolism ; Mice ; Mice, Transgenic ; Neoplasms - genetics ; Neoplasms - immunology ; Neoplasms - metabolism ; Neoplasms - pathology ; Phenotype ; Receptors, KIR - genetics ; Receptors, KIR - metabolism</subject><ispartof>The Journal of immunology (1950), 2015-04, Vol.194 (7), p.3513-3525</ispartof><rights>Copyright © 2015 by The American Association of Immunologists, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c440t-2aa56e53aafc3a18aaf9abf247ead4525cf4173dcb0dc8a3af674ae11634bc043</citedby><cites>FETCH-LOGICAL-c440t-2aa56e53aafc3a18aaf9abf247ead4525cf4173dcb0dc8a3af674ae11634bc043</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25712215$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Katano, Ikumi</creatorcontrib><creatorcontrib>Takahashi, Takeshi</creatorcontrib><creatorcontrib>Ito, Ryoji</creatorcontrib><creatorcontrib>Kamisako, Tsutomu</creatorcontrib><creatorcontrib>Mizusawa, Takuma</creatorcontrib><creatorcontrib>Ka, Yuyo</creatorcontrib><creatorcontrib>Ogura, Tomoyuki</creatorcontrib><creatorcontrib>Suemizu, Hiroshi</creatorcontrib><creatorcontrib>Kawakami, Yutaka</creatorcontrib><creatorcontrib>Ito, Mamoru</creatorcontrib><title>Predominant development of mature and functional human NK cells in a novel human IL-2-producing transgenic NOG mouse</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>We generated a severe immunodeficient NOD/Shi-scid-IL-2Rγ(null) (NOG) mouse substrain expressing the transgenic human IL-2 gene (NOG-IL-2 Tg). Upon transfer of human cord blood-derived hematopoietic stem cells (HSCs), CD3(-)CD56(high)CD16(+/-) cells developed unexpectedly, predominantly in the NOG-IL-2 Tg (hu-HSC NOG-IL-2 Tg). These cells expressed various NK receptors, including NKp30, NKp44, NKp46, NKG2D, and CD94, as well as a diverse set of killer cell Ig-like receptor molecules at levels comparable to normal human NK cells from the peripheral blood, which is evidence of their maturity. They produced levels of granzyme A as high as in human peripheral blood-derived NK cells, and a considerable amount of perforin protein was detected in the plasma. Human NK cells in hu-HSC NOG-IL-2 Tg produced IFN-γ upon stimulation, and IL-2, IL-15, or IL-12 treatment augmented the in vitro cytotoxicity. Inoculation of K562 leukemia cells into hu-HSC NOG-IL-2 Tg caused complete rejection of the tumor cells, whereas inoculation into hu-HSC NOG fully reconstituted with human B, T, and some NK cells did not. Moreover, when a CCR4(+) Hodgkin's lymphoma cell line was inoculated s.c. into hu-HSC NOG-IL-2 Tg, the tumor growth was significantly suppressed by treatment with a therapeutic humanized anti-CCR4 Ab (mogamulizumab), suggesting that the human NK cells in the mice exerted active Ab-dependent cellular cytotoxicity in vivo. Taken together, these data suggest that the new NOG-IL-2 Tg strain is a unique model that can be used to investigate the biological and pathological functions of human NK cells in vivo.</description><subject>Animals</subject><subject>Antibody-Dependent Cell Cytotoxicity</subject><subject>Antigens, Surface - metabolism</subject><subject>Cell Differentiation</subject><subject>Cytotoxicity, Immunologic</subject><subject>Disease Models, Animal</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Hematopoietic Stem Cells - metabolism</subject><subject>Humans</subject><subject>Immunophenotyping</subject><subject>Interleukin-2 - biosynthesis</subject><subject>Interleukin-2 - genetics</subject><subject>Killer Cells, Natural - cytology</subject><subject>Killer Cells, Natural - immunology</subject><subject>Killer Cells, Natural - metabolism</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - immunology</subject><subject>Neoplasms - metabolism</subject><subject>Neoplasms - pathology</subject><subject>Phenotype</subject><subject>Receptors, KIR - genetics</subject><subject>Receptors, KIR - metabolism</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1PwkAQxTdGI4jePZk9einOfhaOhigSCXjQczPdbrGku4vd1sT_3hLAq6eZZN57eZkfIbcMxhLk9GFbOdf5UI-ZBCa4OCNDphQkWoM-J0MAzhOW6nRArmLcAoAGLi_JgKuUcc7UkLRvjS2Cqzz6lhb229Zh52y_h5I6bLvGUvQFLTtv2ip4rOln59DT1Ss1tq4jrTxF6kNvPF4Wy4QnuyYUnan8hrYN-rixvjJ0tZ5TF7por8lFiXW0N8c5Ih_PT--zl2S5ni9mj8vESAltwhGVtkoglkYgm_RzinnJZWqxkIorU0qWisLkUJgJCix1KtEypoXMDUgxIveH3L7OV2djm7kq7mujt32PjE1gknLZv-l_qdZKTjWkupfCQWqaEGNjy2zXVA6bn4xBtseSnbBkRyy95e6Y3uXOFn-GEwfxC71Mi9U</recordid><startdate>20150401</startdate><enddate>20150401</enddate><creator>Katano, Ikumi</creator><creator>Takahashi, Takeshi</creator><creator>Ito, Ryoji</creator><creator>Kamisako, Tsutomu</creator><creator>Mizusawa, Takuma</creator><creator>Ka, Yuyo</creator><creator>Ogura, Tomoyuki</creator><creator>Suemizu, Hiroshi</creator><creator>Kawakami, Yutaka</creator><creator>Ito, Mamoru</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QO</scope><scope>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20150401</creationdate><title>Predominant development of mature and functional human NK cells in a novel human IL-2-producing transgenic NOG mouse</title><author>Katano, Ikumi ; Takahashi, Takeshi ; Ito, Ryoji ; Kamisako, Tsutomu ; Mizusawa, Takuma ; Ka, Yuyo ; Ogura, Tomoyuki ; Suemizu, Hiroshi ; Kawakami, Yutaka ; Ito, Mamoru</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c440t-2aa56e53aafc3a18aaf9abf247ead4525cf4173dcb0dc8a3af674ae11634bc043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Antibody-Dependent Cell Cytotoxicity</topic><topic>Antigens, Surface - metabolism</topic><topic>Cell Differentiation</topic><topic>Cytotoxicity, Immunologic</topic><topic>Disease Models, Animal</topic><topic>Hematopoietic Stem Cell Transplantation</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>Hematopoietic Stem Cells - metabolism</topic><topic>Humans</topic><topic>Immunophenotyping</topic><topic>Interleukin-2 - biosynthesis</topic><topic>Interleukin-2 - genetics</topic><topic>Killer Cells, Natural - cytology</topic><topic>Killer Cells, Natural - immunology</topic><topic>Killer Cells, Natural - metabolism</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - immunology</topic><topic>Neoplasms - metabolism</topic><topic>Neoplasms - pathology</topic><topic>Phenotype</topic><topic>Receptors, KIR - genetics</topic><topic>Receptors, KIR - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Katano, Ikumi</creatorcontrib><creatorcontrib>Takahashi, Takeshi</creatorcontrib><creatorcontrib>Ito, Ryoji</creatorcontrib><creatorcontrib>Kamisako, Tsutomu</creatorcontrib><creatorcontrib>Mizusawa, Takuma</creatorcontrib><creatorcontrib>Ka, Yuyo</creatorcontrib><creatorcontrib>Ogura, Tomoyuki</creatorcontrib><creatorcontrib>Suemizu, Hiroshi</creatorcontrib><creatorcontrib>Kawakami, Yutaka</creatorcontrib><creatorcontrib>Ito, Mamoru</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Katano, Ikumi</au><au>Takahashi, Takeshi</au><au>Ito, Ryoji</au><au>Kamisako, Tsutomu</au><au>Mizusawa, Takuma</au><au>Ka, Yuyo</au><au>Ogura, Tomoyuki</au><au>Suemizu, Hiroshi</au><au>Kawakami, Yutaka</au><au>Ito, Mamoru</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Predominant development of mature and functional human NK cells in a novel human IL-2-producing transgenic NOG mouse</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2015-04-01</date><risdate>2015</risdate><volume>194</volume><issue>7</issue><spage>3513</spage><epage>3525</epage><pages>3513-3525</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>We generated a severe immunodeficient NOD/Shi-scid-IL-2Rγ(null) (NOG) mouse substrain expressing the transgenic human IL-2 gene (NOG-IL-2 Tg). Upon transfer of human cord blood-derived hematopoietic stem cells (HSCs), CD3(-)CD56(high)CD16(+/-) cells developed unexpectedly, predominantly in the NOG-IL-2 Tg (hu-HSC NOG-IL-2 Tg). These cells expressed various NK receptors, including NKp30, NKp44, NKp46, NKG2D, and CD94, as well as a diverse set of killer cell Ig-like receptor molecules at levels comparable to normal human NK cells from the peripheral blood, which is evidence of their maturity. They produced levels of granzyme A as high as in human peripheral blood-derived NK cells, and a considerable amount of perforin protein was detected in the plasma. Human NK cells in hu-HSC NOG-IL-2 Tg produced IFN-γ upon stimulation, and IL-2, IL-15, or IL-12 treatment augmented the in vitro cytotoxicity. Inoculation of K562 leukemia cells into hu-HSC NOG-IL-2 Tg caused complete rejection of the tumor cells, whereas inoculation into hu-HSC NOG fully reconstituted with human B, T, and some NK cells did not. Moreover, when a CCR4(+) Hodgkin's lymphoma cell line was inoculated s.c. into hu-HSC NOG-IL-2 Tg, the tumor growth was significantly suppressed by treatment with a therapeutic humanized anti-CCR4 Ab (mogamulizumab), suggesting that the human NK cells in the mice exerted active Ab-dependent cellular cytotoxicity in vivo. Taken together, these data suggest that the new NOG-IL-2 Tg strain is a unique model that can be used to investigate the biological and pathological functions of human NK cells in vivo.</abstract><cop>United States</cop><pmid>25712215</pmid><doi>10.4049/jimmunol.1401323</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-1767 |
| ispartof | The Journal of immunology (1950), 2015-04, Vol.194 (7), p.3513-3525 |
| issn | 0022-1767 1550-6606 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1808724002 |
| source | MEDLINE; Alma/SFX Local Collection; EZB Electronic Journals Library |
| subjects | Animals Antibody-Dependent Cell Cytotoxicity Antigens, Surface - metabolism Cell Differentiation Cytotoxicity, Immunologic Disease Models, Animal Hematopoietic Stem Cell Transplantation Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - metabolism Humans Immunophenotyping Interleukin-2 - biosynthesis Interleukin-2 - genetics Killer Cells, Natural - cytology Killer Cells, Natural - immunology Killer Cells, Natural - metabolism Mice Mice, Transgenic Neoplasms - genetics Neoplasms - immunology Neoplasms - metabolism Neoplasms - pathology Phenotype Receptors, KIR - genetics Receptors, KIR - metabolism |
| title | Predominant development of mature and functional human NK cells in a novel human IL-2-producing transgenic NOG mouse |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T18%3A10%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Predominant%20development%20of%20mature%20and%20functional%20human%20NK%20cells%20in%20a%20novel%20human%20IL-2-producing%20transgenic%20NOG%20mouse&rft.jtitle=The%20Journal%20of%20immunology%20(1950)&rft.au=Katano,%20Ikumi&rft.date=2015-04-01&rft.volume=194&rft.issue=7&rft.spage=3513&rft.epage=3525&rft.pages=3513-3525&rft.issn=0022-1767&rft.eissn=1550-6606&rft_id=info:doi/10.4049/jimmunol.1401323&rft_dat=%3Cproquest_cross%3E1808724002%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1665496076&rft_id=info:pmid/25712215&rfr_iscdi=true |