Document Detail


The analysis of the functions of human B and T cells in humanized NOD/shi-scid/gammac(null) (NOG) mice (hu-HSC NOG mice).
MedLine Citation:
PMID:  19515798     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
'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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-06-10
Journal Detail:
Title:  International immunology     Volume:  21     ISSN:  1460-2377     ISO Abbreviation:  Int. Immunol.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-23     Completed Date:  2009-09-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8916182     Medline TA:  Int Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  843-58     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan.
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MeSH Terms
Descriptor/Qualifier:
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:
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

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