Dipartimento di Medicina Sperimentale and Centro di Eccellenza per le Ricerche Biomediche, Università degli Studi di Genova, Genoa, Italy.
Blood. 2013 Apr 25;121(17):3396-401. doi: 10.1182/blood-2012-09-458752. Epub 2013 Feb 28.
Natural killer (NK) cells may capture the CCR7 chemokine receptor from allogeneic CCR7(+) cells by trogocytosis and acquire migrating properties in response to lymph node chemokines. This event is negatively regulated by inhibitory killer Ig-like receptors (KIRs) and NKG2A. In this study, we analyzed the role of the HLA-C2-specific activating receptor KIR2DS1 in the process of CCR7 uptake by NK cells interacting with different allogeneic CCR7(+) cells. Co-incubation of KIR2DS1(+) fresh NK cells or NK-cell clones with HLA-C2(+) CCR7(+) lymphoblastoid cell lines resulted in increased CCR7 uptake. Remarkably, KIR2DS1 expression represented a major advantage for acquiring CCR7 from HLA-C2(+) allogeneic dendritic cells (DCs) and T-cell blasts. These findings have important implications in haploidentical hematopoietic stem cell transplantation in which donor-derived (alloreactive) KIR2DS1(+) NK cells, upon CCR7 acquisition, become capable of migrating toward lymph nodes, where they may kill patient DCs and T cells, preventing graft-versus-host and host-versus-graft reactions.
自然杀伤 (NK) 细胞可能通过胞饮作用从同种异体 CCR7(+) 细胞中捕获 CCR7 趋化因子受体，并对淋巴结趋化因子产生迁移特性。这一事件受到抑制性杀伤免疫球蛋白样受体 (KIR) 和 NKG2A 的负调控。在这项研究中，我们分析了 HLA-C2 特异性激活受体 KIR2DS1 在与不同同种异体 CCR7(+) 细胞相互作用的 NK 细胞中摄取 CCR7 的过程中的作用。KIR2DS1(+)新鲜 NK 细胞或 NK 细胞克隆与 HLA-C2(+) CCR7(+)淋巴母细胞系共孵育会导致 CCR7 摄取增加。值得注意的是，KIR2DS1 表达是从 HLA-C2(+)同种异体树突状细胞 (DC) 和 T 细胞母细胞中获得 CCR7 的主要优势。这些发现对单倍体造血干细胞移植具有重要意义，其中供体衍生的（同种反应性）KIR2DS1(+)NK 细胞在获得 CCR7 后，能够向淋巴结迁移，在那里它们可能杀死患者的 DC 和 T 细胞，从而防止移植物抗宿主病和宿主抗移植物反应。
