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Microbial exposure drives polyclonal expansion of innate γδ T cells immediately after birth.
Proceedings of the National Academy of Sciences of the United States of America ( IF 11.1 ) Pub Date : 2020-08-04 , DOI: 10.1073/pnas.1922588117
Sarina Ravens 1, 2 , Alina S Fichtner 3 , Maike Willers 4 , Dennis Torkornoo 3 , Sabine Pirr 4 , Jennifer Schöning 4 , Malte Deseke 3 , Inga Sandrock 3 , Anja Bubke 3 , Anneke Wilharm 3 , Daniel Dodoo , Beverly Egyir 5 , Katie L Flanagan 6, 7, 8, 9 , Lars Steinbrück 10 , Paul Dickinson 11, 12 , Peter Ghazal 12 , Bright Adu 5 , Dorothee Viemann 2, 4, 13 , Immo Prinz 2, 3
Affiliation  

Starting at birth, the immune system of newborns and children encounters and is influenced by environmental challenges. It is still not completely understood how γδ T cells emerge and adapt during early life. Studying the composition of T cell receptors (TCRs) using next-generation sequencing (NGS) in neonates, infants, and children can provide valuable insights into the adaptation of T cell subsets. To investigate how neonatal γδ T cell repertoires are shaped by microbial exposure after birth, we monitored the γ-chain (TRG) and δ-chain (TRD) repertoires of peripheral blood T cells in newborns, infants, and young children from Europe and sub-Saharan Africa. We identified a set of TRG and TRD sequences that were shared by all children from Europe and Africa. These were primarily public clones, characterized by simple rearrangements of Vγ9 and Vδ2 chains with low junctional diversity and usage of non-TRDJ1 gene segments, reminiscent of early ontogenetic subsets of γδ T cells. Further profiling revealed that these innate, public Vγ9Vδ2+ T cells underwent an immediate TCR-driven polyclonal proliferation within the first 4 wk of life. In contrast, γδ T cells using Vδ1+ and Vδ3+ TRD rearrangements did not significantly expand after birth. However, different environmental cues may lead to the observed increase of Vδ1+ and Vδ3+ TRD sequences in the majority of African children. In summary, we show how dynamic γδ TCR repertoires develop directly after birth and present important differences among γδ T cell subsets.



中文翻译:

微生物暴露在出生后立即驱动先天 γδ​​ T 细胞的多克隆扩增。

从出生开始,新生儿和儿童的免疫系统就会遇到环境挑战并受到环境挑战的影响。γδ T 细胞在生命早期是如何出现和适应的仍不完全清楚。使用下一代测序 (NGS) 在新生儿、婴儿和儿童中研究 T 细胞受体 (TCR) 的组成,可以为 T 细胞亚群的适应提供有价值的见解。为了研究新生儿 γδ T 细胞库如何在出生后受到微生物暴露的影响,我们监测了来自欧洲和亚欧的新生儿、婴儿和幼儿外周血 T 细胞的 γ 链 ( TRG ) 和 δ 链 ( TRD ) 库-撒哈拉非洲。我们确定了一组TRGTRD来自欧洲和非洲的所有儿童都共享的序列。这些主要是公共克隆,其特征是 Vγ9 和 Vδ2 链的简单重排,具有低连接多样性和非TRDJ1基因片段的使用,让人联想到 γδ T 细胞的早期个体发育亚群。进一步分析显示,这些先天的、公共的 Vγ9Vδ2 + T 细胞在生命的前 4 周内经历了立即的 TCR 驱动的多克隆增殖。相比之下,使用 Vδ1 +和 Vδ3 + TRD重排的 γδ T 细胞在出生后没有显着扩增。然而,不同的环境线索可能导致观察到的 Vδ1 +和 Vδ3 + TRD增加大多数非洲儿童的序列。总之,我们展示了动态 γδ TCR 库是如何在出生后直接发展的,并呈现 γδ T 细胞亚群之间的重要差异。

更新日期:2020-08-05
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