PMID- 19515798
OWN - NLM
STAT- MEDLINE
DCOM- 20090909
LR  - 20181201
IS  - 1460-2377 (Electronic)
IS  - 0953-8178 (Linking)
VI  - 21
IP  - 7
DP  - 2009 Jul
TI  - The analysis of the functions of human B and T cells in humanized 
      NOD/shi-scid/gammac(null) (NOG) mice (hu-HSC NOG mice).
PG  - 843-58
LID - 10.1093/intimm/dxp050 [doi]
AB  - '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.
FAU - Watanabe, Yohei
AU  - Watanabe Y
AD  - Department of Microbiology and Immunology, Tohoku University Graduate School of 
      Medicine, Aoba-ku, Sendai, Japan.
FAU - Takahashi, Takeshi
AU  - Takahashi T
FAU - Okajima, Akira
AU  - Okajima A
FAU - Shiokawa, Miho
AU  - Shiokawa M
FAU - Ishii, Naoto
AU  - Ishii N
FAU - Katano, Ikumi
AU  - Katano I
FAU - Ito, Ryoji
AU  - Ito R
FAU - Ito, Mamoru
AU  - Ito M
FAU - Minegishi, Masayoshi
AU  - Minegishi M
FAU - Minegishi, Naoko
AU  - Minegishi N
FAU - Tsuchiya, Shigeru
AU  - Tsuchiya S
FAU - Sugamura, Kazuo
AU  - Sugamura K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090610
PL  - England
TA  - Int Immunol
JT  - International immunology
JID - 8916182
RN  - 0 (Antibodies)
RN  - 0 (Antigens, CD34)
RN  - 0 (CD28 Antigens)
RN  - 0 (CD3 Complex)
RN  - 0 (CD40 Antigens)
RN  - 0 (Carrier Proteins)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Interleukin-2)
RN  - 0 (Interleukins)
RN  - 148294-77-3 (noggin protein)
RN  - MKM3CA6LT1 (interleukin-21)
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - Antibodies/immunology
MH  - Antigens, CD34/immunology
MH  - B-Lymphocytes/drug effects/*immunology
MH  - CD28 Antigens/immunology/metabolism
MH  - CD3 Complex/immunology/metabolism
MH  - CD40 Antigens/immunology/metabolism
MH  - Carrier Proteins/genetics/*immunology/metabolism
MH  - Cell Differentiation/immunology
MH  - Fetal Blood/immunology
MH  - Hematopoietic Stem Cells/drug effects/*immunology/metabolism
MH  - Humans
MH  - Immunoglobulin G/biosynthesis/immunology
MH  - Interleukin-2/pharmacology
MH  - Interleukins/pharmacology
MH  - Lymphocyte Activation/immunology
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, Knockout
MH  - Mice, SCID
MH  - Precursor Cells, B-Lymphoid/drug effects/*immunology
MH  - Spleen/drug effects/immunology/metabolism
MH  - T-Lymphocytes/drug effects/*immunology
EDAT- 2009/06/12 09:00
MHDA- 2009/09/10 06:00
CRDT- 2009/06/12 09:00
PHST- 2009/06/12 09:00 [entrez]
PHST- 2009/06/12 09:00 [pubmed]
PHST- 2009/09/10 06:00 [medline]
AID - dxp050 [pii]
AID - 10.1093/intimm/dxp050 [doi]
PST - ppublish
SO  - Int Immunol. 2009 Jul;21(7):843-58. doi: 10.1093/intimm/dxp050. Epub 2009 Jun 10.