The analysis of the functions of human B and T cells in humanized NOD/shi-scid/[gamma]cnull (NOG) mice (hu-HSC NOG mice).
Watanabe, Yohei 1,2; Takahashi, Takeshi 1; Okajima, Akira 1; Shiokawa, Miho 1; Ishii, Naoto 1; Katano, Ikumi 3; Ito, Ryoji 3; Ito, Mamoru 3; Minegishi, Masayoshi 4; Minegishi, Naoko 5; Tsuchiya, Shigeru 2; Sugamura, Kazuo 1
[Article]
International Immunology.
21(7):843-858, July 2009.
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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/[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.
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