Gerosa Franca, Gobbi Andrea, Zorzi Penelope, Burg Stephanie, Briere Francine, Carra Giuseppe, Trinchieri Giorgio
Department of Pathology, Section of Immunology, University of Verona, Verona, Italy.
J Immunol. 2005 Jan 15;174(2):727-34. doi: 10.4049/jimmunol.174.2.727.
A reciprocal activating interaction between NK cells and dendritic cells (DC) has been suggested to play a role in the functional regulation of these cells in immunity, but it has been studied only using in vitro generated bone marrow- or monocyte-derived DC. We report that human peripheral blood plasmacytoid DC (pDC) and myeloid DC are necessary to induce NK cell function depending on the type of microbial stimulus. pDC and myeloid DC are required for strongly increased NK cytolytic activity and CD69 expression, in response to inactivated influenza virus or CpG-containing oligonucleotides and poly(I:C), respectively. Secreted type I IFN is required and sufficient for the augmentation of NK cell cytolytic activity in the coculture with pDC or myeloid DC, whereas CD69 expression is dependent on both type I IFN and TNF. In addition, in response to poly(I:C), myeloid DC induce NK cells to produce IFN-gamma through a mechanism dependent on both IL-12 secretion and cell contact between NK cells and myeloid DC, but independent of type I IFN. IL-2-activated NK cells have little to no cytolytic activity for immature myeloid DC and pDC, but are able to induce maturation of these cells. Moreover, IL-2-activated NK cells induce, in the presence of a suboptimal concentration of CpG-containing oligonucleotides, a strong IFN-alpha and TNF production. These data suggest that the reciprocal functional interaction between NK cells and either pDC or myeloid DC may play an important physiological role in the regulation of both innate resistance and adaptive immunity to infections.
自然杀伤细胞（NK细胞）与树突状细胞（DC）之间的相互激活作用被认为在免疫中对这些细胞的功能调节发挥作用，但此前仅使用体外生成的骨髓来源或单核细胞来源的DC进行过研究。我们报告，根据微生物刺激的类型，人外周血浆细胞样DC（pDC）和髓样DC对于诱导NK细胞功能是必需的。分别响应于灭活流感病毒或含CpG寡核苷酸及聚肌胞苷酸（poly(I:C)），pDC和髓样DC是强烈增加NK细胞溶解活性及CD69表达所必需的。在与pDC或髓样DC共培养中，分泌的I型干扰素对于增强NK细胞溶解活性是必需且足够的，而CD69表达则依赖于I型干扰素和肿瘤坏死因子（TNF）。此外，响应于poly(I:C)，髓样DC通过一种依赖于IL-12分泌以及NK细胞与髓样DC之间细胞接触但独立于I型干扰素的机制诱导NK细胞产生γ干扰素。IL-2激活的NK细胞对未成熟髓样DC和pDC几乎没有或没有细胞溶解活性，但能够诱导这些细胞成熟。此外，IL-2激活的NK细胞在存在次优浓度含CpG寡核苷酸的情况下诱导强烈的α干扰素和TNF产生。这些数据表明，NK细胞与pDC或髓样DC之间的相互功能作用可能在调节对感染的固有抵抗力和适应性免疫中发挥重要的生理作用。
