| RRC ID |
1451
|
| Author |
Harada H, Suzu S, Ito T, Okada S.
|
| Title |
Selective expansion and engraftment of human CD16+ NK cells in NOD/SCID mice.
|
| Journal |
Eur J Immunol
|
| Abstract |
NK cells are large granular lymphocytes that represent a critical component of the innate immunity. Investigations of human NK cell function are largely based on in vitro assays because of the lack of suitable animal models. Here we have established conditions leading to the development of human NK cells in NOD/SCID (severe combined immunodeficiency) mice receiving grafts of cord blood mononuclear cells (CBMC), and GFP-transduced HFWT inducing NK cells (GHINK-1), which have been shown to support the selective expansion of NK cells from human PBMC and CBMC in vitro. Significant numbers of CD56dimCD16+ cytotoxic and CD56-CD16+ immature NK cells appeared in peripheral blood (PB), peritoneal cavity, spleen, bone marrow and liver of the mice. The newly generated NK cells did not express activation markers such as CD25, CD69 and NKp44, the expression of which was augmented by IL-2 in vitro. The NOD/SCID mice engrafted with human NK cells exhibited antitumor activity against K562 erythroleukemia in vitro and in vivo. Thus, we succeeded in developing a CD56dimCD16+ cytotoxic NK cell populations in NOD/SCID mice closely resembling the main NK fraction in human PB and CD56-CD16+ immature NK cells. Our model provides not only information about the development and dynamics of physiological human NK cells but also an important pre-clinical system for immunotherapeutic strategies.
|
| Volume |
35(12)
|
| Pages |
3599-609
|
| Published |
2005-12-1
|
| DOI |
10.1002/eji.200535125
|
| PMID |
16304638
|
| MeSH |
Animals
Antigens, CD / biosynthesis*
Cell Death / immunology
Cell Line, Tumor
Cell Proliferation*
Cells, Cultured
Cytotoxicity, Immunologic*
Fetal Blood / cytology
Fetal Blood / transplantation
GPI-Linked Proteins
Humans
Immunity, Innate
K562 Cells
Killer Cells, Natural / cytology*
Killer Cells, Natural / metabolism
Killer Cells, Natural / transplantation*
Lymphocyte Activation / immunology
Mice
Mice, Inbred NOD
Mice, SCID
Receptors, IgG / biosynthesis*
Transduction, Genetic
|
| IF |
4.404
|
| Times Cited |
12
|
|
WOS Category
|
IMMUNOLOGY
|
| Resource |
| Human and Animal Cells |
K562(RCB0027) |
