| The analysis of the functions of human B and T cells in humanized NOD/shi-scid/gammac(null) (NOG) mice (hu-HSC NOG mice). | |
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MedLine Citation:
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PMID: 19515798 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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'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. |
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Authors:
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Yohei Watanabe; Takeshi Takahashi; Akira Okajima; Miho Shiokawa; Naoto Ishii; Ikumi Katano; Ryoji Ito; Mamoru Ito; Masayoshi Minegishi; Naoko Minegishi; Shigeru Tsuchiya; Kazuo Sugamura |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-06-10 |
Journal Detail:
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Title: International immunology Volume: 21 ISSN: 1460-2377 ISO Abbreviation: Int. Immunol. Publication Date: 2009 Jul |
Date Detail:
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Created Date: 2009-06-23 Completed Date: 2009-09-09 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8916182 Medline TA: Int Immunol Country: England |
Other Details:
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Languages: eng Pagination: 843-58 Citation Subset: IM |
Affiliation:
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Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adoptive Transfer Animals Antibodies / immunology Antigens, CD28 / immunology, metabolism Antigens, CD3 / immunology, metabolism Antigens, CD34 / immunology Antigens, CD40 / immunology, metabolism B-Lymphocytes / drug effects, immunology* Carrier Proteins / genetics, immunology*, metabolism Cell Differentiation / immunology Fetal Blood / immunology Hematopoietic Stem Cells / drug effects, immunology*, metabolism Humans Immunoglobulin G / biosynthesis, immunology Interleukin-2 / pharmacology Interleukins / pharmacology Lymphocyte Activation / immunology Mice Mice, Inbred NOD Mice, Knockout Mice, SCID Precursor Cells, B-Lymphoid / drug effects, immunology* Spleen / drug effects, immunology, metabolism T-Lymphocytes / drug effects, immunology* |
| Chemical | |
Reg. No./Substance:
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0/Antibodies; 0/Antigens, CD28; 0/Antigens, CD3; 0/Antigens, CD34; 0/Antigens, CD40; 0/Carrier Proteins; 0/Immunoglobulin G; 0/Interleukin-2; 0/Interleukins; 0/interleukin-21; 148294-77-3/noggin protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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