Interferon-γ prevents apoptosis in Epstein-Barr virus-infected natural killer cell leukemia in an autocrine fashion
Interferon-γ prevents apoptosis in Epstein-Barr virus-infected natural killer cell leukemia in an autocrine fashion
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DOI：
10.1182/blood.v93.10.3494.410k14_3494_3504
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发表时间：
1999-05-15
期刊：
影响因子：
20.3
通讯作者：
Niho, Y
中科院分区：
文献类型：
--
作者：
Mizuno, S;Akashi, K;Niho, Y
细胞因子的重要功能包括维持细胞存活以及诱导细胞分化和/或增殖。我们在此证明，干扰素-γ (IFN-γ) 通过维持细胞存活，在 Epstein-Barr 病毒 (EBV) 感染的自然杀伤细胞白血病 (NK 白血病) 的进展中发挥作用。从 7 名患者身上获得的 NK 白血病细胞具有克隆性游离型 EBV，表明白血病细胞是克隆来源的。尽管正常NK细胞持续表达Bcl-2，但EBV感染的NK白血病细胞缺乏内源性Bcl-2表达，并且在体外对细胞凋亡高度敏感。向培养物中添加 IFN-γ 显着抑制其自发凋亡，而不诱导细胞增殖或 Bcl-2 上调。 NK白血病细胞持续分泌IFN-γ，患者血清中含有高浓度的IFN-γ，其水平高到足以阻止NK白血病细胞凋亡。 Bcl-X-L 不参与 IFN-γ 诱导的 NK 白血病细胞存活。这些数据表明，除了 Bcl-2 或 BCL-X-L 之外，获得 IFN-γ 介导的自分泌生存信号可能对 EBV 感染的 NK 白血病的发生很重要。 (C) 1999 年，美国血液学会。
The significant function of cytokines includes maintenance of cell survival as well as induction of cell differentiation and/or proliferation. We demonstrate here that interferon-gamma (IFN-gamma) plays a role for progression of Epstein-Barr virus (EBV)-infected natural killer cell leukemia (NK leukemia) through maintaining cell survival. NK leukemia cells obtained from 7 patients had clonal episomal forms of EBV, indicating that the leukemic cells were of clonal origin. Although normal NK cells constitutively expressed Bcl-2, the EBV-infected NK leukemia cells lacked endogenous Bcl-2 expression and were hypersensitive to apoptosis in vitro. The addition of IFN-gamma to the culture significantly inhibited their spontaneous apoptosis without inducing cell proliferation or upregulation of Bcl-2. The NK leukemia cells constitutively secreted IFN-gamma, and the patients' sera contained a high concentration of IFN-gamma, levels that were high enough to prevent NK leukemia cells from apoptosis. Bcl-X-L was not involved in the IFN-gamma-induced NK leukemia cell survival. These data suggest that the acquisition of IFN-gamma-mediated autocrine survival signals, other than Bcl-2 or BCL-X-L, might be important for the development of EBV-infected NK leukemia. (C) 1999 by The American Society of Hematology.