PMID- 19966223
OWN - NLM
STAT- MEDLINE
DCOM- 20100218
LR  - 20211020
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 106
IP  - 51
DP  - 2009 Dec 22
TI  - Expression of human cytokines dramatically improves reconstitution of specific 
      human-blood lineage cells in humanized mice.
PG  - 21783-8
LID - 10.1073/pnas.0912274106 [doi]
AB  - Adoptive transfer of human hematopoietic stem cells (HSCs) into mice lacking T, B 
      and natural killer (NK) cells leads to development of human-blood lineage cells 
      in the recipient mice (humanized mice). Although human B cell reconstitution is 
      robust and T cell reconstitution is reasonable in the recipient mice, 
      reconstitution of NK cells and myeloid cells is generally poor or undetectable. 
      Here, we show that the poor reconstitution is mainly the result of a deficiency 
      of appropriate human cytokines that are necessary for the development and 
      maintenance of these cell lineages. When plasmid DNA encoding human IL-15 and 
      Flt-3/Flk-2 ligand were delivered into humanized mice by hydrodynamic tail-vein 
      injection, the expression of the human cytokine lasted for 2 to 3 weeks and 
      elevated levels of NK cells were induced for more than a month. The 
      cytokine-induced NK cells expressed both activation and inhibitory receptors, 
      killed target cells in vitro, and responded robustly to a virus infection in 
      vivo. Similarly, expression of human GM-CSF and IL-4, macrophage colony 
      stimulating factor, or erythropoietin and IL-3 resulted in significantly enhanced 
      reconstitution of dendritic cells, monocytes/macrophages, or erythrocytes, 
      respectively. Thus, human cytokine gene expression by hydrodynamic delivery is a 
      simple and efficient method to improve reconstitution of specific human-blood 
      cell lineages in humanized mice, providing an important tool for studying human 
      immune responses and disease progression in a small animal model.
FAU - Chen, Qingfeng
AU  - Chen Q
AD  - Interdisciplinary Research Group in Infectious Diseases, Singapore-Massachusetts 
      Institute of Technology Alliance in Research and Technology, S16-05-08, 3 Science 
      Drive 2, Singapore 117543.
FAU - Khoury, Maroun
AU  - Khoury M
FAU - Chen, Jianzhu
AU  - Chen J
LA  - eng
GR  - R01 AI069208/AI/NIAID NIH HHS/United States
GR  - AI69208/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20091204
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Cytokines)
SB  - IM
MH  - Animals
MH  - *Blood Cells
MH  - Cell Lineage
MH  - *Chimera
MH  - Cytokines/*metabolism
MH  - Humans
MH  - Killer Cells, Natural/cytology
MH  - Mice
MH  - Transfection
PMC - PMC2789167
COIS- The authors declare no conflict of interest.
EDAT- 2009/12/08 06:00
MHDA- 2010/02/19 06:00
PMCR- 2009/12/04
CRDT- 2009/12/08 06:00
PHST- 2009/12/08 06:00 [entrez]
PHST- 2009/12/08 06:00 [pubmed]
PHST- 2010/02/19 06:00 [medline]
PHST- 2009/12/04 00:00 [pmc-release]
AID - 0912274106 [pii]
AID - 0694 [pii]
AID - 10.1073/pnas.0912274106 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21783-8. doi: 
      10.1073/pnas.0912274106. Epub 2009 Dec 4.