Cutting edge: Priming of NK cells by IL-18.
Cutting edge: Priming of NK cells by IL-18.
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尖端：IL-18对NK细胞的启动。
DOI：
10.4049/jimmunol.181.3.1627
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发表时间：
2008-08-01
期刊：
影响因子：
--
通讯作者：
Walzer T
中科院分区：
文献类型：
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作者：
Chaix J;Tessmer MS;Hoebe K;Fuséri N;Ryffel B;Dalod M;Alexopoulou L;Beutler B;Brossay L;Vivier E;Walzer T
近期证据表明，自然杀伤（NK）细胞需要经过预激活才能展现出完全的效应活性。在此，我们证实白细胞介素 - 18（IL - 18）促成了这一现象。研究发现，IL - 18信号缺陷型NK细胞在体外受到白细胞介素 - 12（IL - 12）刺激时，无法分泌γ干扰素（IFN - γ）。这并非因为IL - 18具有共刺激作用，因为在体外使用IL - 12刺激时阻断IL - 18信号，并不会改变野生型NK细胞的IFN - γ生成量。相反，我们证明IL - 18在体内对NK细胞进行预激活，使得其在随后受到IL - 12刺激时能够产生IFN - γ。重要的是，IL - 18信号缺陷型和正常的NK细胞在IL - 12诱导下的IFN - γ转录水平相当。这表明IL - 18的预激活作用可促进IFN - γ信使核糖核酸（mRNA）的翻译。这些结果揭示了IL - 12与IL - 18之间一种新型的协同作用，这种作用需要这两种细胞因子按顺序发挥作用。
Recent evidence suggests that NK cells require priming to display full effector activity. Here, we demonstrate that IL-18 contributed to this phenomenon. IL-18 signalling-deficient NK cells were found to be unable to secrete IFN-γ in response to ex vivo stimulation with IL-12. This was not due to a co-stimulatory role of IL-18 because blocking IL-18 signalling during the ex vivo stimulation with IL-12 did not alter IFN-γ production by wild-type NK cells. Rather, we demonstrate that IL-18 primes NK cells in vivo to produce IFN-γ upon subsequent stimulation with IL-12. Importantly, IL-12-induced IFN-γ transcription by NK cells was comparable in IL-18 signalling-deficient and -sufficient NK cells. This suggests that priming by IL-18 leads to an improved translation of IFN-γ mRNA. These results reveal a novel type of cooperation between IL-12 and IL-18 that requires the sequential action of these cytokines.