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
Human and Animal Cells K562(RCB0027)