論文 - 詳細
| RRC ID | 33179 |
|---|---|
| 著者 | Katano I, Takahashi T, Ito R, Kamisako T, Mizusawa T, Ka Y, Ogura T, Suemizu H, Kawakami Y, Ito M. |
| タイトル | Predominant development of mature and functional human NK cells in a novel human IL-2-producing transgenic NOG mouse. |
| ジャーナル | J Immunol |
| 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. |
| 巻・号 | 194(7) |
| ページ | 3513-25 |
| 公開日 | 2015-4-1 |
| DOI | 10.4049/jimmunol.1401323 |
| PII | jimmunol.1401323 |
| PMID | 25712215 |
| MeSH | 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 |
| IF | 4.886 |
| 引用数 | 19 |
| WOS 分野 | IMMUNOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 60 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| 研究用ヒト臍帯血幹細胞 | 研究用ヒト臍帯血幹細胞（CD34陽性細胞） |