PMID- 20027308
OWN - NLM
STAT- MEDLINE
DCOM- 20100317
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 4
IP  - 12
DP  - 2009 Dec 21
TI  - Development of functional human NK cells in an immunodeficient mouse model with 
      the ability to provide protection against tumor challenge.
PG  - e8379
LID - 10.1371/journal.pone.0008379 [doi]
LID - e8379
AB  - Studies of human NK cells and their role in tumor suppression have largely been 
      restricted to in vitro experiments which lack the complexity of whole organisms, 
      or mouse models which differ significantly from humans. In this study we showed 
      that, in contrast to C57BL/6 Rag2(-/-)/gamma(c) (-/-) and NOD/Scid mice, newborn 
      BALB/c Rag2(-/-)/gamma(c) (-/-) mice can support the development of human NK 
      cells and CD56+ T cells after intrahepatic injection with hematopoietic stem 
      cells. The human CD56(+) cells in BALB/c Rag2(-/-)/gamma(c) (-/-) mice were able 
      to produce IFN-gamma in response to human IL-15 and polyI:C. NK cells from 
      reconstituted Rag2(-/-)/gamma(c) (-/-) mice were also able to kill and inhibit 
      the growth of K562 cells in vitro and were able to produce IFN-gamma in response 
      to stimulation with K562 cells. In vivo, reconstituted Rag2(-/-)/gamma(c) (-/-) 
      mice had higher survival rates after K562 challenge compared to non-reconstituted 
      Rag2(-/-)/gamma(c) (-/-) mice and were able to control tumor burden in various 
      organs. Reconstituted Rag2(-/-)/gamma(c) (-/-) mice represent a model in which 
      functional human NK and CD56+ T cells can develop from stem cells and can thus be 
      used to study human disease in a more clinically relevant environment.
FAU - Kwant-Mitchell, Amanda
AU  - Kwant-Mitchell A
AD  - Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, 
      McMaster University Health Sciences Centre, Hamilton, Ontario, Canada.
FAU - Pek, Elishka A
AU  - Pek EA
FAU - Rosenthal, Kenneth L
AU  - Rosenthal KL
FAU - Ashkar, Ali A
AU  - Ashkar AA
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091221
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (CD56 Antigen)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Interleukin Receptor Common gamma Subunit)
RN  - 0 (Rag2 protein, mouse)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Body Weight
MH  - CD56 Antigen/metabolism
MH  - Cell Degranulation
MH  - Cell Proliferation
MH  - Cytotoxicity, Immunologic
MH  - DNA-Binding Proteins/deficiency/metabolism
MH  - Humans
MH  - Immunocompromised Host/*immunology
MH  - Injections
MH  - Interferon-gamma/biosynthesis
MH  - Interleukin Receptor Common gamma Subunit/deficiency/metabolism
MH  - K562 Cells
MH  - Killer Cells, Natural/*cytology/physiology/*transplantation
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Models, Animal
MH  - Neoplasms/*immunology/pathology/*prevention & control
MH  - Survival Analysis
MH  - T-Lymphocytes/cytology/immunology/transplantation
MH  - Tumor Burden/immunology
PMC - PMC2793015
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2009/12/23 06:00
MHDA- 2010/03/18 06:00
PMCR- 2009/12/21
CRDT- 2009/12/23 06:00
PHST- 2009/06/23 00:00 [received]
PHST- 2009/11/22 00:00 [accepted]
PHST- 2009/12/23 06:00 [entrez]
PHST- 2009/12/23 06:00 [pubmed]
PHST- 2010/03/18 06:00 [medline]
PHST- 2009/12/21 00:00 [pmc-release]
AID - 09-PONE-RA-11206R2 [pii]
AID - 10.1371/journal.pone.0008379 [doi]
PST - epublish
SO  - PLoS One. 2009 Dec 21;4(12):e8379. doi: 10.1371/journal.pone.0008379.