PMID- 15920010
OWN - NLM
STAT- MEDLINE
DCOM- 20050929
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 106
IP  - 5
DP  - 2005 Sep 1
TI  - Development of functional human blood and immune systems in NOD/SCID/IL2 receptor 
      gamma chain(null) mice.
PG  - 1565-73
AB  - Here we report that a new nonobese diabetic/severe combined immunodeficient 
      (NOD/SCID) mouse line harboring a complete null mutation of the common cytokine 
      receptor gamma chain (NOD/SCID/interleukin 2 receptor [IL2r] gamma(null)) 
      efficiently supports development of functional human hemato-lymphopoiesis. 
      Purified human (h) CD34(+) or hCD34(+)hCD38(-) cord blood (CB) cells were 
      transplanted into NOD/SCID/IL2rgamma(null) newborns via a facial vein. In all 
      recipients injected with 10(5) hCD34(+) or 2 x 10(4) hCD34(+)hCD38(-) CB cells, 
      human hematopoietic cells were reconstituted at approximately 70% of chimerisms. 
      A high percentage of the human hematopoietic cell chimerism persisted for more 
      than 24 weeks after transplantation, and hCD34(+) bone marrow grafts of primary 
      recipients could reconstitute hematopoiesis in secondary NOD/SCID/IL2rgamma(null) 
      recipients, suggesting that this system can support self-renewal of human 
      hematopoietic stem cells. hCD34(+)hCD38(-) CB cells differentiated into mature 
      blood cells, including myelomonocytes, dendritic cells, erythrocytes, platelets, 
      and lymphocytes. Differentiation into each lineage occurred via developmental 
      intermediates such as common lymphoid progenitors and common myeloid progenitors, 
      recapitulating the steady-state human hematopoiesis. B cells underwent normal 
      class switching, and produced antigen-specific immunoglobulins (Igs). T cells 
      displayed the human leukocyte antigen (HLA)-dependent cytotoxic function. 
      Furthermore, human IgA-secreting B cells were found in the intestinal mucosa, 
      suggesting reconstitution of human mucosal immunity. Thus, the 
      NOD/SCID/IL2rgamma(null) newborn system might be an important experimental model 
      to study the human hemato-lymphoid system.
FAU - Ishikawa, Fumihiko
AU  - Ishikawa F
AD  - Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney 
      St, no. 770, Boston, MA 02115, USA.
FAU - Yasukawa, Masaki
AU  - Yasukawa M
FAU - Lyons, Bonnie
AU  - Lyons B
FAU - Yoshida, Shuro
AU  - Yoshida S
FAU - Miyamoto, Toshihiro
AU  - Miyamoto T
FAU - Yoshimoto, Goichi
AU  - Yoshimoto G
FAU - Watanabe, Takeshi
AU  - Watanabe T
FAU - Akashi, Koichi
AU  - Akashi K
FAU - Shultz, Leonard D
AU  - Shultz LD
FAU - Harada, Mine
AU  - Harada M
LA  - eng
GR  - A130389/PHS HHS/United States
GR  - DK061320/DK/NIDDK NIH HHS/United States
GR  - HL077642/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050526
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, CD34)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Interleukin-2)
RN  - EC 3.2.2.5 (ADP-ribosyl Cyclase)
RN  - EC 3.2.2.5 (CD38 protein, human)
RN  - EC 3.2.2.5 (Cd38 protein, mouse)
RN  - EC 3.2.2.6 (ADP-ribosyl Cyclase 1)
SB  - IM
MH  - ADP-ribosyl Cyclase/immunology
MH  - ADP-ribosyl Cyclase 1
MH  - Animals
MH  - Antigens, CD/immunology
MH  - Antigens, CD34/immunology
MH  - Bone Marrow Cells/cytology/immunology
MH  - *Cord Blood Stem Cell Transplantation
MH  - Disease Models, Animal
MH  - Hematopoietic Stem Cell Transplantation
MH  - Humans
MH  - Immune System/*immunology
MH  - Infant, Newborn
MH  - Membrane Glycoproteins
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, Knockout
MH  - Mice, SCID
MH  - Receptors, Interleukin-2/deficiency/genetics/*immunology/*physiology
MH  - Spleen/cytology/immunology
MH  - Transplantation, Heterologous/immunology
PMC - PMC1895228
EDAT- 2005/05/28 09:00
MHDA- 2005/09/30 09:00
PMCR- 2006/09/01
CRDT- 2005/05/28 09:00
PHST- 2005/05/28 09:00 [pubmed]
PHST- 2005/09/30 09:00 [medline]
PHST- 2005/05/28 09:00 [entrez]
PHST- 2006/09/01 00:00 [pmc-release]
AID - S0006-4971(20)53060-7 [pii]
AID - 01061565 [pii]
AID - 10.1182/blood-2005-02-0516 [doi]
PST - ppublish
SO  - Blood. 2005 Sep 1;106(5):1565-73. doi: 10.1182/blood-2005-02-0516. Epub 2005 May 
      26.