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Microbial exposure drives polyclonal expansion of innate gamma delta T cells immediately after birth

Citation

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]

Copyright Statement

2021 Elsevier Ltd. All rights reserved.

DOI: doi:10.1073/pnas.1922588117

Abstract

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 Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Pharmacology and pharmaceutical sciences
Research Field:Clinical pharmacy and pharmacy practice
Objective Division:Health
Objective Group:Evaluation of health and support services
Objective Field:Evaluation of health outcomes
UTAS Author:Flanagan, K (Dr Katie Flanagan)
ID Code:152642
Year Published:2020
Web of Science® Times Cited:22
Deposited By:Medicine
Deposited On:2022-08-22
Last Modified:2022-09-30
Downloads:0

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