Snoeck H W, Van Bockstaele D R, Nys G, Lenjou M, Lardon F, Haenen L, Rodrigus I, Peetermans M E, Berneman Z N
Laboratory of Experimental Hematology, University of Antwerp (UIA) Antwerp University Hospital (UZA), Edegem, Belgium.
J Exp Med. 1994 Sep 1;180(3):1177-82. doi: 10.1084/jem.180.3.1177.
To assess the effects of interferon gamma (IFN-gamma) on very primitive hematopoietic progenitor cells, CD34(2+)CD38- human bone marrow cells were isolated and cultured in a two-stage culture system, consisting of a primary liquid culture phase followed by a secondary semisolid colony assay. CD34(2+)CD38- cells needed at least the presence of interleukin 3 (IL-3) and kit ligand (KL) together with either IL-1, IL-6, or granulocyte-colony-stimulating factor (G-CSF) in the primary liquid phase in order to proliferate and differentiate into secondary colony-forming cells (CFC). Addition of IFN-gamma to the primary liquid cultures inhibited cell proliferation and generation of secondary CFC in a dose-dependent way. This was a direct effect since it was also seen in primary single cell cultures of CD34(2+)CD38- cells. The proliferation of more mature CD34+CD38+ cells, however, was not inhibited by IFN-gamma, demonstrating for the first time that IFN-gamma is a specific and direct hematopoietic stem cell inhibitor. IFN-gamma, moreover, preserves the viability of CD34(2+)CD38- cells in the absence of other cytokines. IFN-gamma could, therefore, play a role in the protection of the stem cell compartment from exhaustion in situations of hematopoietic stress and may be useful as stem cell protecting agent against chemotherapy for cancer.
为评估干扰素γ（IFN-γ）对极早期造血祖细胞的作用，分离出CD34(2+)CD38-人骨髓细胞，并在两阶段培养系统中培养，该系统包括初级液体培养阶段，随后是次级半固体集落测定。CD34(2+)CD38-细胞在初级液相中至少需要白细胞介素3（IL-3）和干细胞因子（KL）以及IL-1、IL-6或粒细胞集落刺激因子（G-CSF）的存在，才能增殖并分化为次级集落形成细胞（CFC）。在初级液体培养中添加IFN-γ会以剂量依赖的方式抑制细胞增殖和次级CFC的生成。这是一种直接效应，因为在CD34(2+)CD38-细胞的初级单细胞培养中也观察到了这种效应。然而，更成熟的CD34+CD38+细胞的增殖不受IFN-γ的抑制，首次证明IFN-γ是一种特异性的直接造血干细胞抑制剂。此外，在没有其他细胞因子的情况下，IFN-γ可维持CD34(2+)CD38-细胞的活力。因此，IFN-γ在造血应激情况下可能在保护干细胞池免于耗竭方面发挥作用，并且可能作为针对癌症化疗的干细胞保护剂有用。
