Pende Daniela, Castriconi Roberta, Romagnani Paola, Spaggiari Grazia Maria, Marcenaro Stefania, Dondero Alessandra, Lazzeri Elena, Lasagni Laura, Martini Stefania, Rivera Paola, Capobianco Andrea, Moretta Lorenzo, Moretta Alessandro, Bottino Cristina
Istituto Nazionale per la Ricerca sul Cancro, L.go R. Benzi 10, 16132 Genova, Italy.
Blood. 2006 Mar 1;107(5):2030-6. doi: 10.1182/blood-2005-07-2696. Epub 2005 Nov 22.
In this study, we demonstrate the involvement of DNAM-1-triggering receptor and its ligands, poliovirus receptor (PVR) and Nectin-2, in natural killer (NK) cell-mediated lysis of dendritic cells (DCs). The surface expression of both ligands was up-regulated in DCs as compared to monocytes. It reached maximal densities after DC maturation induced by different stimuli including lipopolysaccharide (LPS), poly I:C, flagellin, and CD40L. Both immunohistochemical analysis and confocal microscopy revealed expression of DNAM-1 ligands by DCs in lymph nodes in which they were localized in the parafollicular T-cell region and surrounded the high endothelial venules. Remarkably, in cytolytic assays, DNAM-1 cooperated with NKp30 in the NK-mediated killing of both immature and mature DCs and the degree of contribution of DNAM-1 appeared to correlate with the surface densities of its specific ligands PVR and Nectin-2.
在本研究中,我们证明了DNAX辅助分子-1(DNAM-1)触发受体及其配体脊髓灰质炎病毒受体(PVR)和Nectin-2参与自然杀伤(NK)细胞介导的树突状细胞(DC)裂解。与单核细胞相比,DC中两种配体的表面表达均上调。在由不同刺激物(包括脂多糖(LPS)、聚肌苷酸:聚胞苷酸(poly I:C)、鞭毛蛋白和CD40L)诱导的DC成熟后,其密度达到最大值。免疫组织化学分析和共聚焦显微镜检查均显示,DC在淋巴结中表达DNAM-1配体,它们位于滤泡旁T细胞区并围绕高内皮小静脉。值得注意的是,在细胞溶解试验中,DNAM-1与NKp30协同作用于NK介导的未成熟和成熟DC的杀伤,并且DNAM-1的贡献程度似乎与其特异性配体PVR和Nectin-2的表面密度相关。