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  • Title: Generation of natural killer cells from Thy 1.1+ bone marrow precursor cells in the rat.
    Author: van den Brink MR, Herberman RB, Hiserodt JC.
    Journal: Blood; 1991 Nov 01; 78(9):2392-5. PubMed ID: 1681963.
    Abstract:
    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.
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