Suppression of normal human erythropoiesis by gamma interferon in vitro. Role of monocytes and T lymphocytes.
Suppression of normal human erythropoiesis by gamma interferon in vitro. Role of monocytes and T lymphocytes.
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DOI：
10.1172/jci111853
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发表时间：
1985-05
期刊：
影响因子：
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通讯作者：
S. W. Mamus;S. Beck-Schroeder;E. Zanjani
中科院分区：
文献类型：
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作者：
S. W. Mamus;S. Beck-Schroeder;E. Zanjani
干扰素（IFN）已显示在体外抑制人红系祖细胞（红系爆发形成单位[BFU-E]和集落形成单位[CFU-E]）的增殖。为了研究这种抑制活性的机制，研究了不同剂量（50- 10，000 U）的重组DNA产生的人γ-IFN的高度纯化制剂在存在和不存在单核细胞和/或T淋巴细胞的情况下对正常人骨髓BFU-E和CFU-E的红系集落形成的影响。向全骨髓中加入γ-IFN以剂量依赖性方式引起BFU-E（6-65%）和CFU-E（31-79%）的抑制。直接向培养板中加入γ-IFN以及用γ-IFN预孵育骨髓细胞，然后洗涤细胞，均可产生这种抑制作用;在最高浓度的γ-IFN（10，000 U）下，仅预暴露15 min，就可产生对集落形成的接近最大抑制作用（BFU-E，50%; CFU-E，81%）。在加入γ-IFN之前去除单核细胞和/或T淋巴细胞显著降低了这种淋巴因子的抑制作用（BFU-E，-1至38%; CFU-E，-8至67%）。纯化的自体单核细胞或T细胞预暴露于γ-IFN与单核细胞和T细胞耗尽的骨髓细胞的共培养导致红系细胞集落形成的高度显着的抑制，即使当这些处理的细胞包括小于1%的总有核细胞群体的文化。γ-IFN的抑制作用不能被促红细胞生成素阻止或逆转。这些结果表明，γ-干扰素对红细胞生成的抑制作用介导的辅助细胞群体，在很大程度上，并建议γ-干扰素可能是一个有用的工具，在免疫活性细胞在体外红细胞生成的调节作用的研究。
Interferons (IFN) have been shown to suppress the proliferation of human erythroid progenitors (erythroid burst-forming units [BFU-E] and colony-forming units [CFU-E]) in vitro. To examine the mechanism(s) underlying this inhibitory activity, the effect of different doses (50-10,000 U) of a highly purified preparation of recombinant DNA produced human gamma-IFN on erythroid colony formation by normal human bone marrow BFU-E and CFU-E in the presence and absence of monocytes and/or T lymphocytes was studied. The addition of gamma-IFN to whole marrow caused suppression of BFU-E (6-65%) and CFU-E (31-79%) in a dose-dependent fashion. This inhibition occurred both with the direct addition of gamma-IFN to the culture plates as well as by the preincubation of marrow cells with gamma-IFN followed by the washing of the cells; at the highest concentration of gamma-IFN (10,000 U), near-maximal inhibition of colony formation occurred with as little as 15 min of preexposure (BFU-E, 50%; CFU-E, 81%). Removal of monocytes and/or T lymphocytes before the addition of gamma-IFN significantly reduced the inhibitory effects of this lymphokine (BFU-E, -1 to 38%; CFU-E, -8 to 67%). Co-culture of purified autologous monocytes or T cells preexposed to gamma-IFN with monocyte and T cell-depleted marrow cells resulted in highly significant inhibition of erythroid colony formation even when these treated cells comprised less than 1% of the total nucleated cell populations in culture. The inhibitory action of gamma-IFN was not prevented or reversed by erythropoietin. These results demonstrate that the inhibitory effects of gamma-IFN on erythropoiesis are mediated to a significant degree through accessory cell populations, and suggest that gamma-IFN may represent a useful tool in the study of the role of immunocompetent cells in the regulation of erythropoiesis in vitro.