Cytokine-induced memory-like natural killer cells
Cytokine-induced memory-like natural killer cells
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DOI：
10.1073/pnas.0813192106
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发表时间：
2009-02-10
影响因子：
11.1
通讯作者：
Yokoyama, Wayne M.
中科院分区：
文献类型：
--
作者：
Cooper, Megan A.;Elliott, Julie M.;Yokoyama, Wayne M.
哺乳动物对感染的免疫应答由两个广泛的分支介导，即先天免疫系统和适应性免疫系统。先天免疫细胞是抵抗病原体的第一线防御，并且被认为对感染有一致的反应，而不管先前的暴露，即，它们不表现出对先前激活的记忆。相比之下，适应性免疫细胞显示具有2个基本特征的免疫记忆，抗原特异性和随后暴露时的放大反应。而适应性免疫细胞具有重排的受体基因以识别抗原的宇宙，自然杀伤（NK）细胞是先天免疫淋巴细胞，具有用于靶识别的有限的种系编码受体库。NK细胞还产生细胞因子如IFN-γ（IFN-γ）以在对感染的先天性应答期间保护宿主。在此，我们表明，转移到幼稚宿主中的精氨酸激活的NK细胞可以在7-22天后特异性检测到，此时它们与幼稚细胞表型相似并且不组成性产生IFN-γ。然而，当再刺激时，它们产生显著更多的IFN-γ。这种类似记忆的特性是NK细胞固有的。相比之下，记忆样NK细胞不表达颗粒酶B蛋白，并且与初始NK细胞类似地杀死靶。因此，这些实验鉴定了先天免疫细胞保留先前激活的内在记忆的能力，该功能直到现在仅归因于抗原特异性适应性免疫细胞。免疫学
The mammalian immune response to infection is mediated by 2 broad arms, the innate and adaptive immune systems. Innate immune cells are a first-line defense against pathogens and are thought to respond consistently to infection, regardless of previous exposure, i.e., they do not exhibit memory of prior activation. By contrast, adaptive immune cells display immunologic memory that has 2 basic characteristics, antigen specificity and an amplified response upon subsequent exposure. Whereas adaptive immune cells have rearranged receptor genes to recognize the universe of antigens, natural killer (NK) cells are innate immune lymphocytes with a limited repertoire of germ-line encoded receptors for target recognition. NK cells also produce cytokines such as IFN-gamma (IFN-gamma) to protect the host during the innate response to infection. Herein, we show that cytokine-activated NK cells transferred into naive hosts can be specifically detected 7-22 days later when they are phenotypically similar to naive cells and are not constitutively producing IFN-gamma. However, they produce significantly more IFN-gamma when restimulated. This memory-like property is intrinsic to the NK cell. By contrast, memory-like NK cells do not express granzyme B protein and kill targets similarly to naive NK cells. Thus, these experiments identify an ability of innate immune cells to retain an intrinsic memory of prior activation, a function until now attributed only to antigen-specific adaptive immune cells. IMMUNOLOGY