Generation of natural killer cells from Thy 1.1+ bone marrow precursor cells in the rat.
We have recently described a long-term bone marrow culture (LTBMC) system in the rat for the generation of natural killer (NK) cells from bone marrow (BM) precursors in the presence of interleukin-2 (IL-2). We found that the LTBMC-conditioned medium was essential to render the NK precursor cells responsive to IL-2. In this report, we isolated by flow cytometric cell sorting Thy 1.1+ BM cells, which have been shown to contain pluripotent stem cells and early precursor cells of various hematopoietic lineages. These Thy 1.1+ immature BM precursors did not generate any detectable NK activity when cultured for 7 days with IL-2 alone. However, when the cells were cultured with IL-2 in the presence of LTBMC-conditioned medium, NK cells were generated as demonstrated by cytolytic activity against NK-sensitive tumor targets, large granular lymphocyte (LGL) morphology, and the acquisition of NK cell-associated phenotype (72% of the cells were 3.2.3+/OX41-/CD5-). This study demonstrates the existence of an IL-2 unresponsive Thy 1.1+ NK precursor in the BM of the rat, that can differentiate to a mature NK cell in the presence of LTBMC-conditioned medium and IL-2.
Pittsburgh Cancer Institute, PA 15213.
M R
MR
van den Brink
R B
RB
Herberman
J C
JC
Hiserodt
D000818:Animals; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000032:analysis*; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002469:Cell Separation; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D018800:Thy-1 Antigens
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007376:Interleukin-2; D018800:Thy-1 Antigens