Skip Navigation


International Immunology Advance Access originally published online on June 10, 2009
International Immunology 2009 21(7):843-858; doi:10.1093/intimm/dxp050
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
21/7/843    most recent
dxp050v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Watanabe, Y.
Right arrow Articles by Sugamura, K.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Watanabe, Y.
Right arrow Articles by Sugamura, K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?


© The Japanese Society for Immunology. 2009. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

The analysis of the functions of human B and T cells in humanized NOD/shi-scid/{gamma}cnull (NOG) mice (hu-HSC NOG mice)

Yohei Watanabe1,2, Takeshi Takahashi1, Akira Okajima1, Miho Shiokawa1, Naoto Ishii1, Ikumi Katano3, Ryoji Ito3, Mamoru Ito3, Masayoshi Minegishi4, Naoko Minegishi5, Shigeru Tsuchiya2 and Kazuo Sugamura1

1 Department of Microbiology and Immunology
2 Department of Pediatrics, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan
3 Laboratory of Immunology, Central Institute for Experimental Animals, 1430 Nogawa, Miyamae-ku, Kawasaki 216-0001, Japan
4 Division of Blood Transfusion, Tohoku University Hospital, 2-1 Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan
5 Department of Health and Welfare Science, Sendai University, 2-2-18 Funaokaminami, Shibata-machi, Miyagi-ken 989-1693, Japan

Correspondence to: T. Takahashi; E-mail: takeshi-takahashi{at}mail.tains.tohoku.ac.jp

‘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/{gamma}cnull (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.

Keywords: adaptive immunity, humanized mice, NOG mice, thymus

Transmitting editor: K. Yamamoto

Received 13 March 2009, accepted 1 May 2009.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.