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

Yohei Watanabe, Takeshi Takahashi, Akira Okajima, Miho Shiokawa, Naoto Ishii, Ikumi Katano, Ryoji Ito, Mamoru Ito, Masayoshi Minegishi, Naoko Minegishi, Shigeru Tsuchiya, Kazuo Sugamura

Research output: Contribution to journalArticlepeer-review

129 Citations (Scopus)

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/γcnull (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.

Original languageEnglish
Pages (from-to)843-858
Number of pages16
JournalInternational immunology
Volume21
Issue number7
DOIs
Publication statusPublished - 2009

Keywords

  • Adaptive immunity
  • Humanized mice
  • NOG mice
  • Thymus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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