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Microbial exposure drives polyclonal expansion of innate gamma delta T cells immediately after birth
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.
History
Publication title
Proceedings of the National Academy of Sciences of the United States of AmericaVolume
117Issue
31Pagination
18649-18660ISSN
0027-8424Department/School
Tasmanian School of MedicinePublisher
Natl Acad SciencesPlace of publication
2101 Constitution Ave Nw, Washington, USA, Dc, 20418Rights statement
© 2021 Elsevier Ltd. All rights reserved.Repository Status
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