Department of Immunology, Imperial College, Chelsea & Westminster Hospital, London, UK.
Sensors (Basel). 2009;9(1):386-403. doi: 10.3390/s90100386. Epub 2009 Jan 9.
Human plasmacytoid dendritic cells secrete high levels of IFNα and are thus implicated in the activation of NK cells. Activated NK cells are characterised by the up-regulation of CD69 and MHC class II DR expression, secretion of IFN γ and enhanced cytotoxicity. We show that pDC mediate these processes by different mechanisms, some of which overlap. Human NK cells were analysed after co-culture with immature or CpG-matured blood pDC or with supernatant from these cells. Maximal CD69 expression by NK cells was mediated by supernatant from mature pDC and did not require pDC contact. Up-regulation was due in part to IFNα but also to factors in IFNα negative supernatant from immature DC. HLA-DR expression was independent of secreted molecules but required contact with immature or mature DC. Enhanced NK cytotoxicity, measured by killing of K562 targets and expression of CD107a, was mediated by multiple factors including type I IFN, supernatant from immature pDC cultures and contact with immature or mature pDC. These factors act cumulatively to enhance cytotoxcity. Thus different parameters of pDC mediated NK cell activation are regulated by distinct pathways.
人浆细胞样树突状细胞（pDC）分泌高水平的 IFNα，因此被认为在 NK 细胞的激活中起作用。激活的 NK 细胞的特征是上调 CD69 和 MHC Ⅱ类 DR 的表达、IFNγ 的分泌和增强的细胞毒性。我们发现 pDC 通过不同的机制介导这些过程，其中一些机制是重叠的。在与未成熟或 CpG 成熟的血液 pDC 共培养或与这些细胞的上清液共培养后，分析人 NK 细胞。NK 细胞的最大 CD69 表达是由成熟 pDC 的上清液介导的，不需要 pDC 接触。上调部分是由于 IFNα，但也由于未成熟 DC 的 IFNα 阴性上清液中的因子。HLA-DR 的表达不依赖于分泌的分子，但需要与未成熟或成熟的 DC 接触。通过杀伤 K562 靶细胞和表达 CD107a 来衡量的增强的 NK 细胞毒性，是由多种因素介导的，包括 I 型 IFN、未成熟 pDC 培养上清液和与未成熟或成熟 pDC 的接触。这些因素共同作用增强细胞毒性。因此，pDC 介导的 NK 细胞激活的不同参数受不同途径的调节。
