Yang Liping, Dybedal Ingunn, Bryder David, Nilsson Lars, Sitnicka Ewa, Sasaki Yutaka, Jacobsen Sten Eirik W
Hemopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden.
J Immunol. 2005 Jan 15;174(2):752-7. doi: 10.4049/jimmunol.174.2.752.
Whereas multiple growth-promoting cytokines have been demonstrated to be involved in regulation of the hemopoietic stem cell (HSC) pool, the potential role of negative regulators is less clear. However, IFN-gamma, if overexpressed, can mediate bone marrow suppression and has been directly implicated in a number of bone marrow failure syndromes, including graft-vs-host disease. Whether IFN-gamma might directly affect the function of repopulating HSCs has, however, not been investigated. In the present study, we used in vitro conditions promoting self-renewing divisions of human HSCs to investigate the effect of IFN-gamma on HSC maintenance and function. Although purified cord blood CD34(+)CD38(-) cells underwent cell divisions in the presence of IFN-gamma, cycling HSCs exposed to IFN-gamma in vitro were severely compromised in their ability to reconstitute long-term cultures in vitro and multilineage engraft NOD-SCID mice in vivo (>90% reduced activity in both HSC assays). In vitro studies suggested that IFN-gamma accelerated differentiation of targeted human stem and progenitor cells. These results demonstrate that IFN-gamma can negatively affect human HSC self-renewal.
尽管多种促生长细胞因子已被证明参与造血干细胞（HSC）库的调节，但负调节因子的潜在作用尚不清楚。然而，γ干扰素若过度表达，可介导骨髓抑制，并直接与包括移植物抗宿主病在内的多种骨髓衰竭综合征有关。然而，γ干扰素是否可能直接影响再植造血干细胞的功能尚未得到研究。在本研究中，我们利用促进人造血干细胞自我更新分裂的体外条件，研究γ干扰素对造血干细胞维持和功能的影响。尽管纯化的脐血CD34(+)CD38(-)细胞在γ干扰素存在下进行细胞分裂，但体外暴露于γ干扰素的循环造血干细胞在体外重建长期培养物以及在体内多谱系植入NOD-SCID小鼠的能力严重受损（在两种造血干细胞检测中活性降低>90%）。体外研究表明，γ干扰素加速了靶向人干细胞和祖细胞的分化。这些结果表明，γ干扰素可对人造血干细胞的自我更新产生负面影响。
