論文 - 詳細
| RRC ID | 19299 |
|---|---|
| 著者 | Watanabe Y, Takahashi T, Okajima A, Shiokawa M, Ishii N, Katano I, Ito R, Ito M, Minegishi M, Minegishi N, Tsuchiya S, Sugamura K. |
| タイトル | The analysis of the functions of human B and T cells in humanized NOD/shi-scid/gammac(null) (NOG) mice (hu-HSC NOG mice). |
| ジャーナル | Int Immunol |
| Abstract |
'Humanized mice' are anticipated to be a valuable tool for studying the human immune system, but the reconstituted human immune cells have not yet been well characterized. Here, we extensively investigated the differentiation and functions of human B and T cells in a supra-immunodeficient mouse strain, NOD/shi-scid/gammac(null) (NOG) reconstituted with CD34(+) hematopoietic stem cells obtained from umbilical cord blood. In these hu-HSC NOG mice, the development of human B cells was partially blocked, and a significant number of B-cell progenitors accumulated in the spleen. The mature CD19(+)IgM(+)IgD(+) human B cells of the hu-HSC NOG mice could produce IgG in vivo and in vitro by antigenic stimulation. In contrast, although human T cells with an apparently normal phenotype developed, most of them could neither proliferate nor produce IL-2 in response to antigenic stimulation by anti-CD3 and anti-CD28 antibodies in vitro. The positive selection of human T cells in the thymus was sufficiently functional, if not complete, and mainly mediated by mouse class II, suggesting that the human T cells lost their function in the periphery. We found that multiple mechanisms were involved in the T-cell abnormalities. Collectively, our results demonstrate that further improvements are necessary before humanized mice with a functional human immune system are achieved. |
| 巻・号 | 21(7) |
| ページ | 843-58 |
| 公開日 | 2009-7-1 |
| DOI | 10.1093/intimm/dxp050 |
| PII | dxp050 |
| PMID | 19515798 |
| MeSH | Adoptive Transfer Animals Antibodies / immunology Antigens, CD34 / immunology B-Lymphocytes / drug effects B-Lymphocytes / immunology* CD28 Antigens / immunology CD28 Antigens / metabolism CD3 Complex / immunology CD3 Complex / metabolism CD40 Antigens / immunology CD40 Antigens / metabolism Carrier Proteins / genetics Carrier Proteins / immunology* Carrier Proteins / metabolism Cell Differentiation / immunology Fetal Blood / immunology Hematopoietic Stem Cells / drug effects Hematopoietic Stem Cells / immunology* Hematopoietic Stem Cells / metabolism Humans Immunoglobulin G / biosynthesis Immunoglobulin G / immunology Interleukin-2 / pharmacology Interleukins / pharmacology Lymphocyte Activation / immunology Mice Mice, Inbred NOD Mice, Knockout Mice, SCID Precursor Cells, B-Lymphoid / drug effects Precursor Cells, B-Lymphoid / immunology* Spleen / drug effects Spleen / immunology Spleen / metabolism T-Lymphocytes / drug effects T-Lymphocytes / immunology* |
| IF | 3.519 |
| 引用数 | 122 |
| 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 | 31 |
| 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 | 臍帯血 |