Markers of nonselective and specific NK cell activation.
Markers of nonselective and specific NK cell activation.
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DOI：
10.4049/jimmunol.1202533
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发表时间：
2013-06-15
期刊：
影响因子：
--
通讯作者：
French AR
中科院分区：
文献类型：
--
作者：
Fogel LA;Sun MM;Geurs TL;Carayannopoulos LN;French AR
NK 细胞的激活由来自细胞因子受体和种系编码的激活和抑制受体的信号整合控制。 NK 细胞在 MCMV 感染期间经历两个不同的激活阶段：由促炎细胞因子介导的非选择性阶段和由 Ly49H 信号驱动的特定阶段，Ly49H 是一种识别感染细胞的 NK 细胞激活受体。我们试图描绘出能够区分非选择性激活的 NK 细胞和通过 NK 细胞受体特异性激活的细胞表面标记。我们证明，Sca-1 在病毒感染期间高度上调（甚至比 CD69 还要高），并可作为早期非选择性 NK 细胞激活的新标志物。事实上，在 MCMV 感染期间，与 Sca-1− NK 细胞相比，更多比例的 Sca-1+ NK 细胞产生 IFN-γ。与 MCMV 感染早期 NK 细胞上 Sca-1（以及 KLRG1）普遍上调相反，在 MCMV 感染后期，在 Ly49H+ 和 Ly49H− NK 细胞上观察到 Sca-1 以及 CD27 和 KLRG1 的差异表达。在表达 Ly49H 的 NK 细胞上观察到在 Sca-1 和 CD27 下调的背景下 KLRG1 水平持续升高。此外，这些细胞表面标志物的差异表达模式取决于 Ly49H 对其配体的识别，并且不仅仅由于细胞增殖而发生。这些发现表明，Sca-1、CD27 和 KLRG1 的组合可以区分被细胞因子非选择性激活的 NK 细胞和通过激活受体特异性刺激的 NK 细胞。
NK cell activation is controlled by the integration of signals from cytokine receptors and germ-line encoded activation and inhibitory receptors. NK cells undergo two distinct phases of activation during MCMV infection: a nonselective phase mediated by pro-inflammatory cytokines and a specific phase driven by signaling through Ly49H, an NK cell activation receptor that recognizes infected cells. We sought to delineate cell surface markers that could distinguish NK cells that had been activated nonselectively from those that had been specifically activated through NK cell receptors. We demonstrated that Sca-1 is highly upregulated during viral infections (to an even greater extent than CD69) and serves as a novel marker of early, nonselective NK cell activation. Indeed, a greater proportion of Sca-1+ NK cells produced IFN-γ compared to Sca-1− NK cells during MCMV infection. In contrast to the universal upregulation of Sca-1 (as well as KLRG1) on NK cells early during MCMV infection, differential expression of Sca-1, as well as CD27 and KLRG1, was observed on Ly49H+ and Ly49H− NK cells late during MCMV infection. Persistently elevated levels of KLRG1 in the context of down regulation of Sca-1 and CD27 were observed on NK cells that expressed Ly49H. Furthermore, the differential expression patterns of these cell surface markers were dependent on Ly49H recognition of its ligand and did not occur solely as a result of cellular proliferation. These findings demonstrate that a combination of Sca-1, CD27, and KLRG1 can distinguish NK cells nonselectively activated by cytokines from those specifically stimulated through activation receptors.
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