TUMOR-NECROSIS-FACTOR-ALPHA COOPERATES WITH INTERLEUKIN-3 IN THE RECRUITMENT OF A PRIMITIVE SUBSET OF HUMAN CD34+ PROGENITORS
TUMOR-NECROSIS-FACTOR-ALPHA COOPERATES WITH INTERLEUKIN-3 IN THE RECRUITMENT OF A PRIMITIVE SUBSET OF HUMAN CD34+ PROGENITORS
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DOI：
10.1084/jem.177.6.1815
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发表时间：
1993-06-01
影响因子：
15.3
通讯作者：
BANCHEREAU, J
中科院分区：
文献类型：
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作者：
CAUX, C;DURAND, I;BANCHEREAU, J
我们最近已经证明，肿瘤坏死因子α（TNF-α）增强白细胞介素3（IL-3）和粒细胞/巨噬细胞集落刺激因子诱导的CD 34+造血祖细胞（HPC）的生长，并有利于树突状细胞/朗格汉斯细胞的产生。在本研究中详细描述了TNF-α的刺激作用。因此，在用IL-3脉冲48小时后进入循环（S/G2 M）的CD 34 + HPC表达转铁蛋白受体（TfR），并且荧光激活的细胞分选器分离的TfR+ HPC而不是TfR-HPC显示出对IL-3的高增殖反应。相比之下，发现TfR-HPC响应于IL-3 + TNF-α而经历强增殖。有限稀释实验表明，TNF-α增加了由TfR-HPC产生的克隆的频率和平均大小，这是由于产生了更多数量的大克隆。相反，TNF-α并不增强TfR+ HPC的IL-3依赖性增殖。用TNF-α预培养CD 34 + HPC 48 h可增强随后产生的IL-3依赖性集落形成单位。用TNF-α预培养或用次优剂量的TNF-α培养允许募集具有粒细胞和单核细胞分化潜能的细胞。两者合计，我们的研究结果表明，TNF-α招聘的CD 34 + HPC低敏感的IL-3亚群，具有高增殖能力和多能祖细胞的一些功能，这可能是更原始的比那些单独响应IL-3。
We have recently demonstrated that tumor necrosis factor alpha (TNF-alpha) potentiates interleukin 3 (IL-3)- and granulocyte/macrophage colony-stimulating factor-induced growth of CD34+ hematopoietic progenitor cells (HPC), and favors the generation of dendritic/Langerhans cells. The stimulatory effect of TNF-alpha was detailed in the present study. Thus, CD34+ HPC entering in cycle (S/G2M) after a 48-h pulse with IL-3 expressed the transferrin receptor (TfR), and fluorescence-activated cell sorter-separated TfR+ HPC, but not TfR- HPC, showed a high proliferative response to IL-3. In contrast, TfR- HPC were found to undergo strong proliferation in response to IL-3 + TNF-alpha. Limiting dilution experiments indicated that TNF-alpha increased both the frequency and the average size of clones generated from TfR- HPC as a result of the development of a higher number of large clones. In contrast, TNF-alpha did not enhance the IL-3-dependent proliferation of TfR+ HPC. Preculturing CD34+ HPC for 48 h with TNF-alpha enhanced the subsequent generation of IL-3-dependent colony-forming units. Precultures with TNF-alpha or cultures with suboptimal doses of TNF-alpha allowed the recruitment of cells with both granulocytic and monocytic differentiation potential. Taken together, our results indicate that TNF-alpha recruits a subpopulation of CD34+ HPC hyposensitive to IL-3, with high proliferative capacity and some features of multipotential progenitors, that are likely to be more primitive than those responding to IL-3 alone.