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Concomitant assessment of PD-1 and CD56 expression identifies subsets of resting cord blood Vδ2 T cells with disparate cytotoxic potential
Cellular Immunology ( IF 4.3 ) Pub Date : 2023-12-23 , DOI: 10.1016/j.cellimm.2023.104797
Haoting Hsu , Claudio Zanettini , Modupe Coker , Sarah Boudova , David Rach , Godfrey Mvula , Titus H. Divala , Randy G. Mungwira , Francesca Boldrin , Giulia Degiacomi , Laura Cioetto Mazzabò , Riccardo Manganelli , Miriam K. Laufer , Yuji Zhang , Luigi Marchionni , Cristiana Cairo

Vγ9Vδ2 T lymphocytes are programmed for broad antimicrobial responses with rapid production of Th1 cytokines even before birth, and thus thought to play key roles against pathogens in infants. The process regulating Vδ2 cell acquisition of cytotoxic potential shortly after birth remains understudied. We observed that perforin production in cord blood Vδ2 cells correlates with phenotypes defined by the concomitant assessment of PD-1 and CD56. Bulk RNA sequencing of sorted Vδ2 cell fractions indicated that transcripts related to cytotoxic activity and NK function are enriched in the subset with the highest proportion of perforin+ cells. Among differentially expressed transcripts, IRF8, previously linked to CD8 T cell effector differentiation and NK maturation, has the potential to mediate Vδ2 cell differentiation towards cytotoxic effectors. Our current and past results support the hypothesis that distinct mechanisms regulate Vδ2 cell cytotoxic function before and after birth, possibly linked to different levels of microbial exposure.



中文翻译:

PD-1 和 CD56 表达的同时评估可识别具有不同细胞毒性潜力的静息脐带血 Vδ2 T 细胞亚群

Vγ9Vδ2 T 淋巴细胞被编程为广泛的抗菌反应,甚至在出生前就快速产生 Th1 细胞因子,因此被认为在对抗婴儿病原体方面发挥着关键作用。Vδ2 细胞在出生后不久获得细胞毒性潜力的调节过程仍有待研究。我们观察到,脐带血 Vδ2 细胞中穿孔素的产生与同时评估 PD-1 和 CD56 所定义的表型相关。对分选的 Vδ2 细胞组分进行批量 RNA 测序表明,与细胞毒活性和 NK 功能相关的转录物在穿孔素+细胞比例最高的子集中富集。在差异表达的转录本中,IRF8先前与 CD8 T 细胞效应器分化和 NK 成熟相关,具有介导 Vδ2 细胞向细胞毒性效应器分化的潜力。我们当前和过去的结果支持这样的假设:不同的机制在出生前后调节 Vδ2 细胞的细胞毒功能,可能与不同水平的微生物暴露有关。

更新日期:2023-12-23
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