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

Ravens S, Fichtner AS, Willers M, Torkornoo D, Pirr S, Schoening J, Deseke M, Sandrock I, Bubke A, Wilharm A, Dodoo D, Egyir B, Flanagan KL, Steinbrueck L, Dickinson P, Ghazal P, Adu B, Viemann D, Prinz I (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Proceedings of the National Academy of Sciences of the United States of America National Academy of Sciences

Book Volume: 117

Pages Range: 18649-18660

Journal Issue: 31

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 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. Thesewere 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.

Involved external institutions

Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) University of Ghana GH Ghana (GH) London School of Hygiene and Tropical Medicine GB United Kingdom (GB) University of Edinburgh GB United Kingdom (GB)

How to cite

APA:

Ravens, S., Fichtner, A.S., Willers, M., Torkornoo, D., Pirr, S., Schoening, J.,... Prinz, I. (2020). 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, 117(31), 18649-18660. https://doi.org/10.1073/pnas.1922588117

MLA:

Ravens, Sarina, et al. "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 117.31 (2020): 18649-18660.

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