Martín-Fontecha Alfonso, Thomsen Lindy L, Brett Sara, Gerard Craig, Lipp Martin, Lanzavecchia Antonio, Sallusto Federica
Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland.
Nat Immunol. 2004 Dec;5(12):1260-5. doi: 10.1038/ni1138. Epub 2004 Nov 7.
Naive T cells are stimulated by antigen-presenting dendritic cells (DCs) in secondary lymphoid organs, but whether other types of cell participate in T cell priming is unclear. Here we show in mice that natural killer (NK) cells, which are normally excluded from lymph nodes, are rapidly recruited in a CCR7-independent, CXCR3-dependent manner to lymph nodes on stimulation by the injection of mature DCs. Recruitment of NK cells is also induced by some, but not all, adjuvants and correlates with the induction of T helper cell type 1 (T(H)1) responses. NK cell depletion and reconstitution experiments show that NK cells provide an early source of interferon-gamma (IFN-gamma) that is necessary for T(H)1 polarization. Taken together, our results identify an induced pathway of NK cell migration in antigen-stimulated lymph nodes and a mechanism by which some adjuvants may facilitate T(H)1 responses.
初始T细胞在二级淋巴器官中由抗原呈递树突状细胞(DC)刺激,但其他类型的细胞是否参与T细胞启动尚不清楚。我们在小鼠中发现,通常被排除在淋巴结之外的自然杀伤(NK)细胞,在注射成熟DC刺激后,以不依赖CCR7、依赖CXCR3的方式迅速被招募到淋巴结。一些但不是所有的佐剂也能诱导NK细胞的募集,并且这与1型辅助性T细胞(TH1)反应的诱导相关。NK细胞耗竭和重建实验表明,NK细胞提供了TH1极化所必需的早期干扰素-γ(IFN-γ)来源。综上所述,我们的结果确定了抗原刺激的淋巴结中NK细胞迁移的诱导途径,以及一些佐剂促进TH1反应的机制。