Ximena León-Lara, Alina S Fichtner, Maike Willers, Tao Yang, Katharina Schaper, Lennart Riemann, Jennifer Schöning, Anna Harms, Vicente Almeida, Anja Schimrock, Anika Janssen, Laura Ospina-Quintero, Constantin von Kaisenberg, Reinhold Förster, Matthias Eberl, Manuela F Richter, Sabine Pirr, Dorothee Viemann, Sarina Ravens
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引用次数: 0
摘要
早产儿患新生儿败血症的风险很高。γδT细胞被认为是新生儿中一组重要的效应细胞。在这里,我们使用新一代测序、流式细胞术和功能测试对早产新生儿纵向队列中的γδT细胞进行了研究。在新生儿出生后的第一年,Vγ9Vδ2 T细胞亚群表现出动态的表型变化,在患有败血症的婴儿中,胎儿来源的Vγ9Vδ2 T细胞水平明显升高。单细胞转录组学发现,新生儿败血症中的HLA-DRhiCD83+ γδ T细胞表达与抗原递呈相关的基因。体外试验显示,CD83 在早产儿和足月新生儿活化的 Vγ9Vδ2 T 细胞上表达,但在成人中没有表达。相反,激活成人 Vγ9Vδ2 T 细胞会增强 CD86 的表达,CD86 可能是诱导 CD4 T 细胞增殖的关键受体。总之,我们提供了早产后γδT细胞成熟的图谱,并强调了它们在感染中的表型多样性。
γδ T cell profiling in a cohort of preterm infants reveals elevated frequencies of CD83+ γδ T cells in sepsis.
Preterm infants are at high risk of developing neonatal sepsis. γδ T cells are thought to be an important set of effector cells in neonates. Here, γδ T cells were investigated in a longitudinal cohort of preterm neonates using next-generation sequencing, flow cytometry, and functional assays. During the first year of life, the Vγ9Vδ2 T cell subset showed dynamic phenotypic changes and elevated levels of fetal-derived Vγ9Vδ2 T cells were evident in infants with sepsis. Single-cell transcriptomics identified HLA-DRhiCD83+ γδ T cells in neonatal sepsis, which expressed genes related to antigen presentation. In vitro assays showed that CD83 was expressed on activated Vγ9Vδ2 T cells in preterm and term neonates, but not in adults. In contrast, activation of adult Vγ9Vδ2 T cells enhanced CD86 expression, which was presumably the key receptor to induce CD4 T cell proliferation. Together, we provide a map of the maturation of γδ T cells after preterm birth and highlight their phenotypic diversity in infections.
期刊介绍:
Since its establishment in 1896, the Journal of Experimental Medicine (JEM) has steadfastly pursued the publication of enduring and exceptional studies in medical biology. In an era where numerous publishing groups are introducing specialized journals, we recognize the importance of offering a distinguished platform for studies that seamlessly integrate various disciplines within the pathogenesis field.
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