Regulatory NK cells suppress antigen-specific T cell responses
Regulatory NK cells suppress antigen-specific T cell responses
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DOI：
10.4049/jimmunol.180.2.850
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发表时间：
2008-01-15
影响因子：
4.4
通讯作者：
Akdis, Mubeccel
中科院分区：
文献类型：
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作者：
Deniz, Gunnur;Erten, Gaye;Akdis, Mubeccel
免疫系统有多种调节/抑制过程，这些过程对发展对过敏原的健康或过敏免疫反应具有决定性作用。与Th1和Th2细胞类似，NK1和NK2亚群已被证明在免疫反应中发挥反调节和激发作用。在过去的十年中，抑制Th1和Th2应答的T调节细胞一直是密集研究的焦点。在这项研究中，我们的目的是通过根据NK细胞分泌IL-10的特性来表征NK细胞亚群，从而研究人类的调节性NK细胞。新鲜纯化的分泌IL-10的NK细胞表达的IL-10增加了40倍，但不表达FoxP3和转化生长因子-β的mRNAs。PHA和IL-2刺激以及维生素D3/地塞米松和抗CD2/CD16单抗可诱导NK细胞表达IL-10。在蜂毒主要变应原磷脂酶A(2-)和牛分枝杆菌纯化蛋白衍生物诱导的T细胞增殖中，检测了IL-10(+)NK细胞对抗原特异性T细胞增殖的影响。IL-10+NK细胞显著抑制变应原/抗原诱导的T细胞增殖和IL-13和干扰素-γ的分泌，尤其是通过阻断IL-10受体而分泌IL-10。这些结果表明，在人类中，有一小部分NK细胞具有调节功能。
The immune system has a variety of regulatory/suppressive processes, which are decisive for the development of a healthy or an allergic immune response to allergens. NK1 and NK2 subsets have been demonstrated to display counterregulatory and provocative roles in immune responses, similar to Th1 and Th2 cells. T regulatory cells suppressing both Th1 and Th2 responses have been the focus of intensive research during the last decade. In this study, we aimed to investigate regulatory NK cells in humans, by characterization of NK cell subsets according to their IL-10 secretion property. Freshly purified IL-10-secreting NK cells expressed up to 40-fold increase in IL-10, but not in the FoxP3 and TGF-beta mRNAs. PHA and IL-2 stimulation as well as vitamin D3/dexamethasone and anti-CD2/CD16 mAbs are demonstrated to induce IL-10 expression in NK cells. The effect of IL-10(+) NK cells on Ag-specific T cell proliferation has been examined in bee venom major allergen, phospholipase A(2-) and purified protein derivative of Mycobecterium bovis-induced T cell proliferation. IL-10+ NK cells significantly suppressed both allergen/Ag-induced T cell proliferation and secretion of IL-13 and IFN-gamma, particularly due to secreted IL-10 as demonstrated by blocking of the IL-10 receptor. These results demonstrate that a distinct small fraction of NK cells display regulatory functions in humans.