Institute of Immunity & Transplantation, UCL, London, NW3 2PP, UK.
Department of Surgery, UCL, Royal Free Campus, London, NW3 2PF, UK.
Nat Commun. 2023 Mar 14;14(1):1409. doi: 10.1038/s41467-023-37181-w.
Natural killer cells are considered to be important for control of human cytomegalovirus- a major pathogen in immune suppressed transplant patients. Viral infection promotes the development of an adaptive phenotype in circulating natural killer cells that changes their anti-viral function. In contrast, less is understood how natural killer cells that reside in tissue respond to viral infection. Here we show natural killer cells resident in the liver have an altered phenotype in cytomegalovirus infected individuals and display increased anti-viral activity against multiple viruses in vitro and identify and characterise a subset of natural killer cells responsible for control. Crucially, livers containing natural killer cells with better capacity to control cytomegalovirus replication in vitro are less likely to experience viraemia post-transplant. Taken together, these data suggest that virally induced expansion of tissue resident natural killer cells in the donor organ can reduce the chance of viraemia post-transplant.
自然杀伤细胞被认为对控制人类巨细胞病毒(一种免疫抑制移植患者的主要病原体)很重要。病毒感染促进了循环自然杀伤细胞中适应性表型的发展,改变了它们的抗病毒功能。相比之下,人们对驻留在组织中的自然杀伤细胞如何对病毒感染作出反应了解较少。在这里,我们表明,在巨细胞病毒感染个体中,肝脏中驻留的自然杀伤细胞具有改变的表型,并在体外显示出对多种病毒的增强抗病毒活性,并鉴定和表征负责控制的自然杀伤细胞亚群。至关重要的是,含有在体外具有更好控制巨细胞病毒复制能力的自然杀伤细胞的肝脏,在移植后发生病毒血症的可能性较小。总之,这些数据表明,供体器官中受病毒诱导的组织驻留自然杀伤细胞的扩增可以降低移植后病毒血症的机会。