期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 31, 页码 18649-18660出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1922588117
关键词
TRG and TRD repertoires; neonatal gamma delta T cells; postnatal TCR repertoire focusing; V gamma 9V delta 2; non-V gamma 9V delta 2
资金
- German Research Foundation Deutsche Forschungsgemeinschaft (DFG) under Germany's Excellence Strategy [EXC 2155, 390874280, SFB900, 158989968]
- DFG [FOR2799, RA3077/1-1, PR727/11-1]
- UK Medical Research Council (MRC) [G0701291]
- MRC [SCC1085]
Starting at birth, the immune system of newborns and children encounters and is influenced by environmental challenges. It is still not completely understood how gamma delta 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 gamma delta T cell repertoires are shaped by microbial exposure after birth, we monitored the gamma-chain (TRG) and delta-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 V gamma 9 and V delta 2 chains with low junctional diversity and usage of nonTRDJ1 gene segments, reminiscent of early ontogenetic subsets of gamma delta T cells. Further profiling revealed that these innate, public V gamma 9V delta 2(+) T cells underwent an immediate TCR-driven polyclonal proliferation within the first 4 wk of life. In contrast, gamma delta T cells using V delta 1(+) and V delta 3+ TRD rearrangements did not significantly expand after birth. However, different environmental cues may lead to the observed increase of V delta 1(+) and V delta 3(+) TRD sequences in the majority of African children. In summary, we show how dynamic gamma delta TCR repertoires develop directly after birth and present important differences among gamma delta T cell subsets.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据