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Int Immunol. 2009 Jul;21(7):843-58. doi: 10.1093/intimm/dxp050. Epub 2009 Jun 10.

The analysis of the functions of human B and T cells in humanized NOD/shi-scid/gammac(null) (NOG) mice (hu-HSC NOG mice).

Author information

1
Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan.

Abstract

'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.

PMID:
19515798
DOI:
10.1093/intimm/dxp050
[Indexed for MEDLINE]

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