Szabolcs P, Avigan D, Gezelter S, Ciocon D H, Moore M A, Steinman R M, Young J W
Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York 10021-6399, USA.
Blood. 1996 Jun 1;87(11):4520-30.
CD34+ precursors in normal human bone marrow (BM) generate large numbers of dendritic cells alongside macrophages and granulocytic precursors when cultured for 12 to 14 days in c-kit ligand, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha). This study reports an intermediate cell type that develops by day 6, and has the potential to differentiate into either macrophages or dendritic cells. When the d6 progeny are depleted of mature macrophages and residual CD34+ precursors, a discrete CD14+ HLA-DR+ population persists in addition to immunostimulatory CD14- HLA-DR() dendritic cells. Half of the CD14+ HLA-DR+ population is in cell cycle (Ki-67+), but colony-forming units (CFUs) are no longer detectable. The calls are c-fms+, but lack myeloperoxidase and nonspecific esterase. They also possess substantial phagocytic and allostimulatory activity. These post-CFU, CD14+ HLA-DR+ intermediates develop into typical macrophages when recultured in the absence of exogenous cytokines. M-CSF supports up to approximately 2.5-fold expansion of macrophage progeny. In contrast, the combination of GM-CSF and TNF-alpha supports quantitative differentiation into dendritic cells, lacking c-fms, CD14, and other macrophage properties, and expressing HLA-DR, CD1a, CD83, CD80, CD86, and potent allostimulatory activity. Therefore, normal CD34+ BM precursors can generate a post-CFU bipotential intermediate in the presence of c-kit ligand, GM-CSF, and TNF-alpha. This intermediate cell type will develop along the dendritic cell pathway when macrophages are removed and GM-CSF and TNF-alpha are provided. Alternatively, it can differentiate along a macrophage pathway when recultured with or without M-CSF.
正常人骨髓中的CD34+前体细胞在含有c-kit配体、粒细胞-巨噬细胞集落刺激因子（GM-CSF）和肿瘤坏死因子-α（TNF-α）的培养基中培养12至14天时，可生成大量树突状细胞，同时还有巨噬细胞和粒细胞前体。本研究报告了一种在第6天出现的中间细胞类型，它有可能分化为巨噬细胞或树突状细胞。当第6天的子代细胞中成熟巨噬细胞和残留的CD34+前体细胞被去除后，除了具有免疫刺激作用的CD14-HLA-DR（）树突状细胞外，还存在一个离散的CD14+HLA-DR+群体。CD14+HLA-DR+群体中有一半处于细胞周期（Ki-67+），但集落形成单位（CFU）已无法检测到。这些细胞c-fms+，但缺乏髓过氧化物酶和非特异性酯酶。它们还具有较强的吞噬和异体刺激活性。当在无外源性细胞因子的条件下重新培养时，这些CFU后、CD14+HLA-DR+中间细胞会发育成典型的巨噬细胞。M-CSF可使巨噬细胞子代细胞数量最多扩增约2.5倍。相比之下，GM-CSF和TNF-α的组合可支持细胞定量分化为树突状细胞，这些树突状细胞缺乏c-fms、CD14和其他巨噬细胞特性，表达HLA-DR、CD1a、CD83、CD80、CD86，并具有强大的异体刺激活性。因此，在c-kit配体、GM-CSF和TNF-α存在的情况下，正常的CD34+骨髓前体细胞可生成一种CFU后双潜能中间细胞。当去除巨噬细胞并提供GM-CSF和TNF-α时，这种中间细胞类型将沿着树突状细胞途径发育。或者，当在有或无M-CSF的情况下重新培养时，它可沿着巨噬细胞途径分化。
