Ravens, S and Fichtner, AS and Willers, M and Torkornoo, D and Pirr, S and Deseke, M and Sandrock, I and Bubke, A and Wilharm, A and Dodoo, D and Egyir, B and Flanagan, K and Steinbruck, L and Dickinson, P and Ghazal, P and Adu, B and Viemann, D and Prinz, I and Schoening, J, Microbial exposure drives polyclonal expansion of innate gamma delta T cells immediately after birth, Proceedings of the National Academy of Sciences of the United States of America, 117, (31) pp. 18649-18660. ISSN 0027-8424 (2020) [Refereed Article]
© 2021 Elsevier Ltd. All rights reserved.
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.
|Item Type:||Refereed Article|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Pharmacology and pharmaceutical sciences|
|Research Field:||Clinical pharmacy and pharmacy practice|
|Objective Group:||Evaluation of health and support services|
|Objective Field:||Evaluation of health outcomes|
|UTAS Author:||Flanagan, K (Dr Katie Flanagan)|
|Web of Science® Times Cited:||22|
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