Engraftment of human myelodysplastic syndrome derived cell line in transgenic severe combined immunodeficient (TG-SCID) mice expressing human GM-CSF and IL-3.
A transgenic SCID (TG-SCID) mouse expressing the human cytokines interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) has been generated with the aim of making a model system allowing the in vivo proliferation of human hematopoietic cells. Using TG-SCID mice expressing high levels (30-35 ng/ml in the serum) of human GM-CSF and IL-3, we attempted to engraft a human myeloid leukemia cell line, F-36P, derived from a myelodysplastic syndrome (MDS) patient. When F-36P cells were transferred intravenously into sublethally irradiated TG-SCID mice, extensive proliferation of F-36P cells was found 4-6 wk later. Successful engraftment, however, required the preadministration of a monoclonal antibody to mouse interleukin-2 receptor (IL-2R) beta chain, neutralizing NK activity. Surprisingly, all the transplanted TG-SCID mice engrafted with F-36P cells developed hind leg paralysis approximately 6 wk after transfer. Histological analysis demonstrated extensive invasion and formation of osteolytic lesions by the F-36P cells in the vertebrae. These data indicate that transgenic SCID mice expressing human IL-3 and GM-CSF provide a useful system for the study of human leukemia. In addition, NK cells appear to play an important role in rejection of human cells.
Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba Science-city, Ibaraki, Japan.
D K
DK
Kim
M
M
Kojima
T
T
Fukushima
M
M
Miyasaka
H
H
Nakauchi
D000818:Animals; D016207:Cytokines / Q000502:physiology; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics*; D006801:Humans; D007377:Interleukin-3 / Q000096:biosynthesis* / Q000235:genetics*; D007694:Killer Cells, Natural / Q000502:physiology; D007951:Leukemia, Myeloid; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology*; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous / Q000276:immunology*; D014407:Tumor Cells, Cultured
D016207:Cytokines; D007377:Interleukin-3; D016178:Granulocyte-Macrophage Colony-Stimulating Factor