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International Immunology Advance Access published online on June 10, 2009
International Immunology, doi:10.1093/intimm/dxp050
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© 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: 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.


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