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

Article Authors:Yohei Watanabe; Takeshi Takahashi; Akira Okajima; Miho Shiokawa; Naoto Ishii; Ikumi Katano; Ryoji Ito; Mamoru Ito; Masayoshi Minegishi; Naoko Minegishi; Shigeru Tsuchiya; Kazuo Sugamura
Article Title:The analysis of the functions of human B and T cells in humanized NOD/shi-scid/gammac(null) (NOG) mice (hu-HSC NOG mice).
Reference Detail
Reference ID:1025933
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.
Affiliations:Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan.
Reference Type:Literature
PubMed ID:19515798
Journal:Int Immunol
Journal Volume:21
Article Pages:843-58
Journal ISSN:1460-2377
Article Chemical List:Antibodies;Antigens, CD28;Antigens, CD3;Antigens, CD34;Antigens, CD40;Carrier Proteins;Immunoglobulin G;Interleukin-2;Interleukins;interleukin-21;noggin protein
Article MeSH List:Adoptive Transfer; Animals; Antibodies(immunology); Antigens, CD28(immunology; metabolism); Antigens, CD3(immunology; metabolism); Antigens, CD34(immunology); Antigens, CD40(immunology; metabolism); B-Lymphocytes(drug effects; immunology); Carrier Proteins(genetics; immunology; metabolism); Cell Differentiation(immunology); Fetal Blood(immunology); Hematopoietic Stem Cells(drug effects; immunology; metabolism); Humans; Immunoglobulin G(biosynthesis; immunology); Interleukin-2(pharmacology); Interleukins(pharmacology); Lymphocyte Activation(immunology); Mice; Mice, Inbred NOD; Mice, Knockout; Mice, SCID; Precursor Cells, B-Lymphoid(drug effects; immunology); Spleen(drug effects; immunology; metabolism); T-Lymphocytes(drug effects; immunology)
Curation Last Updated:2014-10-03 22:54:32