RRC ID 37792
Author Watanabe Y, Takahashi T, Okajima A, Shiokawa M, Ishii N, Katano I, Ito R, Ito M, Minegishi M, Minegishi N, Tsuchiya S, Sugamura K.
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).
Journal Int. Immunol.
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.
Volume 21(7)
Pages 843-58
Published 2009-7
DOI 10.1093/intimm/dxp050
PII dxp050
PMID 19515798
MeSH Adoptive Transfer Animals Antibodies / immunology Antigens, CD34 / immunology B-Lymphocytes / drug effects B-Lymphocytes / immunology* CD28 Antigens / immunology CD28 Antigens / metabolism CD3 Complex / immunology CD3 Complex / metabolism CD40 Antigens / immunology CD40 Antigens / metabolism Carrier Proteins / genetics Carrier Proteins / immunology* Carrier Proteins / metabolism Cell Differentiation / immunology Fetal Blood / immunology Hematopoietic Stem Cells / drug effects Hematopoietic Stem Cells / immunology* Hematopoietic Stem Cells / metabolism Humans Immunoglobulin G / biosynthesis Immunoglobulin G / immunology Interleukin-2 / pharmacology Interleukins / pharmacology Lymphocyte Activation / immunology Mice Mice, Inbred NOD Mice, Knockout Mice, SCID Precursor Cells, B-Lymphoid / drug effects Precursor Cells, B-Lymphoid / immunology* Spleen / drug effects Spleen / immunology Spleen / metabolism T-Lymphocytes / drug effects T-Lymphocytes / immunology*
IF 5.189
Times Cited 84
WOS Category IMMUNOLOGY
Resource
Human and Animal Cells