The transcription factor interferon regulatory factor-1 is essential for natural killer cell function in vivo.
The transcription factor interferon regulatory factor-1 is essential for natural killer cell function in vivo.
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DOI：
10.1084/jem.184.5.2043
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发表时间：
1996-11-01
期刊：
影响因子：
--
通讯作者：
Mak TW
中科院分区：
文献类型：
--
作者：
Duncan GS;Mittrücker HW;Kägi D;Matsuyama T;Mak TW
自然杀伤(NK)细胞是一种细胞毒性淋巴细胞，具有主要组织相容性复合体(MHC)的无限制杀伤和早期抗病毒防御能力，其激活与小鼠病毒感染中干扰素(IFN)-α/β的增加有关。I型干扰素(干扰素-α/β)在初次病毒感染后早期在多种细胞中表达，并已被证明介导了对各种病毒的耐药性。本研究探讨了转录激活剂干扰素调节因子-1(IRF-1)对小鼠NK细胞活性的影响。IRF-1基因缺陷小鼠显示出正常频率的NK标记阳性细胞，但在病毒感染和干扰素诱导剂Polyinosinic：Polycytidiic Actidiic体内刺激后，NK细胞介导的细胞毒作用显著降低。在体外，在干扰素-β、IL-2和IL-12刺激下，IRF-1缺陷的NK细胞的杀伤活性仍然存在缺陷。IRF-1基因缺陷的小鼠无法在体内消除同基因MHC I类阴性肿瘤细胞，并降低了从循环中排斥亲代半异基因供体细胞的能力。因此，IRF-1对于诱导NK细胞介导的细胞毒作用以及由这种活性介导的体内效应功能是必不可少的。
The activation of natural killer (NK) cells, cytotoxic lymphocytes capable of major histocompatibility complex (MHC)-unrestricted killing and early antiviral defense, is temporally related to the increased interferon (IFN)-alpha/beta production that is seen in the viral infection of mice. Type I IFN (IFN-alpha/beta) are expressed in many cell types early after primary viral infection and have been shown to mediate resistance against a variety of viruses. In this study, the role of the transcriptional activator IFN regulatory factor-1 (IRF-1) in murine NK cell activity was assessed. IRF-1-deficient mice displayed a normal frequency of NK marker-positive cells, but exhibited greatly reduced NK cell-mediated cytotoxicity after both virus infection and stimulation with the IFN inducer polyinosinic:polycytidilic acid in vivo. In vitro, cytolytic activity in IRF-1-deficient NK cells remained defective after stimulation with IFN-beta, IL-2, and IL-12. IRF-1- deficient mice were unable to eliminate syngeneic MHC class I-negative tumor cells in vivo, and had a reduced ability to reject parental semi- allogeneic donor cells from the circulation. Thus, IRF-1 is essential for the induction of NK cell-mediated cytotoxicity and for the in vivo effector functions that are mediated by this activity.
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影响因子：
11.4
作者：
REIS, LFL;RUFFNER, H;WEISSMANN, C
通讯作者：
WEISSMANN, C
影响因子：
64.8
作者：
KAGI, D;LEDERMANN, B;HENGARTNER, H
通讯作者：
HENGARTNER, H
影响因子：
3.7
作者：
XIAO, L;ENEROTH, PHE;QURESHI, GA
通讯作者：
QURESHI, GA
影响因子：
--
作者：
Trinchieri G
通讯作者：
Trinchieri G
影响因子：
64.8
作者：
LOWIN, B;HAHNE, M;TSCHOPP, J
通讯作者：
TSCHOPP, J