Adema G J, Hartgers F, Verstraten R, de Vries E, Marland G, Menon S, Foster J, Xu Y, Nooyen P, McClanahan T, Bacon K B, Figdor C G
Department of Tumour Immunology, University Hospital Nijmegen, The Netherlands.
Nature. 1997 Jun 12;387(6634):713-7. doi: 10.1038/42716.
Dendritic cells form a system of highly efficient antigen-presenting cells. After capturing antigen in the periphery, they migrate to lymphoid organs where they present the antigen to T cells. Their seemingly unique ability to interact with and sensitize naive T cells gives dendritic cells a central role in the initiation of immune responses and allows them to be used in therapeutic strategies against cancer, viral infection and other diseases. How they interact preferentially with naive rather than activated T lymphocytes is still poorly understood. Chemokines direct the transport of white blood cells in immune surveillance. Here we report the identification and characterization of a C-C chemokine (DC-CK1) that is specifically expressed by human dendritic cells at high levels. Tissue distribution analysis demonstrates that dendritic cells present in germinal centres and T-cell areas of secondary lymphoid organs express this chemokine. We show that DC-CK1, in contrast to RANTES, MIP-1alpha and interleukin-8, preferentially attracts naive T cells (CD45RA+). The specific expression of DC-CK1 by dendritic cells at the site of initiation of an immune response, combined with its chemotactic activity for naive T cells, suggests that DC-CK1 has an important rule in the induction of immune responses.
树突状细胞构成了一个高效的抗原呈递细胞系统。在外周捕获抗原后,它们迁移至淋巴器官,在那里将抗原呈递给T细胞。树突状细胞与初始T细胞相互作用并使其致敏的独特能力,使其在免疫反应启动中发挥核心作用,并使其能够应用于针对癌症、病毒感染及其他疾病的治疗策略。然而,它们如何优先与初始T淋巴细胞而非活化T淋巴细胞相互作用,目前仍知之甚少。趋化因子在免疫监视中指导白细胞的运输。在此,我们报告一种C-C趋化因子(DC-CK1)的鉴定及特性,该趋化因子在人树突状细胞中高水平特异性表达。组织分布分析表明,存在于次级淋巴器官生发中心和T细胞区的树突状细胞表达这种趋化因子。我们发现,与RANTES、MIP-1α和白细胞介素-8不同,DC-CK1优先吸引初始T细胞(CD45RA+)。树突状细胞在免疫反应起始部位特异性表达DC-CK1,再加上其对初始T细胞的趋化活性,表明DC-CK1在免疫反应诱导中具有重要作用。