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

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Microbial exposure drives polyclonal expansion of innate γδ T cells immediately after birth. / Ravens, Sarina; Fichtner, Alina S; Willers, Maike; Torkornoo, Dennis; Pirr, Sabine; Schöning, Jennifer; Deseke, Malte; Sandrock, Inga; Bubke, Anja; Wilharm, Anneke; Dodoo, Daniel; Egyir, Beverly; Flanagan, Katie L; Steinbrück, Lars; Dickinson, Paul; Ghazal, Peter; Adu, Bright; Viemann, Dorothee; Prinz, Immo.

In: P NATL ACAD SCI USA, Vol. 117, No. 31, 04.08.2020, p. 18649-18660.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Ravens, S, Fichtner, AS, Willers, M, Torkornoo, D, Pirr, S, Schöning, J, Deseke, M, Sandrock, I, Bubke, A, Wilharm, A, Dodoo, D, Egyir, B, Flanagan, KL, Steinbrück, L, Dickinson, P, Ghazal, P, Adu, B, Viemann, D & Prinz, I 2020, 'Microbial exposure drives polyclonal expansion of innate γδ T cells immediately after birth', P NATL ACAD SCI USA, vol. 117, no. 31, pp. 18649-18660. https://doi.org/10.1073/pnas.1922588117

APA

Ravens, S., Fichtner, A. S., Willers, M., Torkornoo, D., Pirr, S., Schöning, J., Deseke, M., Sandrock, I., Bubke, A., Wilharm, A., Dodoo, D., Egyir, B., Flanagan, K. L., Steinbrück, L., Dickinson, P., Ghazal, P., Adu, B., Viemann, D., & Prinz, I. (2020). Microbial exposure drives polyclonal expansion of innate γδ T cells immediately after birth. P NATL ACAD SCI USA, 117(31), 18649-18660. https://doi.org/10.1073/pnas.1922588117

Vancouver

Ravens S, Fichtner AS, Willers M, Torkornoo D, Pirr S, Schöning J et al. Microbial exposure drives polyclonal expansion of innate γδ T cells immediately after birth. P NATL ACAD SCI USA. 2020 Aug 4;117(31):18649-18660. https://doi.org/10.1073/pnas.1922588117

Bibtex

@article{65059df00541469aba6cd05e25e4dea2,
title = "Microbial exposure drives polyclonal expansion of innate γδ T cells immediately after birth",
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. These were 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.",
keywords = "Africa South of the Sahara, Bacteria/immunology, Child, Child, Preschool, Europe, Gene Rearrangement, T-Lymphocyte/genetics, Humans, Infant, Infant, Newborn, Longitudinal Studies, Receptors, Antigen, T-Cell, gamma-delta/genetics, T-Lymphocyte Subsets/immunology",
author = "Sarina Ravens and Fichtner, {Alina S} and Maike Willers and Dennis Torkornoo and Sabine Pirr and Jennifer Sch{\"o}ning and Malte Deseke and Inga Sandrock and Anja Bubke and Anneke Wilharm and Daniel Dodoo and Beverly Egyir and Flanagan, {Katie L} and Lars Steinbr{\"u}ck and Paul Dickinson and Peter Ghazal and Bright Adu and Dorothee Viemann and Immo Prinz",
year = "2020",
month = aug,
day = "4",
doi = "10.1073/pnas.1922588117",
language = "English",
volume = "117",
pages = "18649--18660",
journal = "P NATL ACAD SCI USA",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "31",

}

RIS

TY - JOUR

T1 - Microbial exposure drives polyclonal expansion of innate γδ T cells immediately after birth

AU - Ravens, Sarina

AU - Fichtner, Alina S

AU - Willers, Maike

AU - Torkornoo, Dennis

AU - Pirr, Sabine

AU - Schöning, Jennifer

AU - Deseke, Malte

AU - Sandrock, Inga

AU - Bubke, Anja

AU - Wilharm, Anneke

AU - Dodoo, Daniel

AU - Egyir, Beverly

AU - Flanagan, Katie L

AU - Steinbrück, Lars

AU - Dickinson, Paul

AU - Ghazal, Peter

AU - Adu, Bright

AU - Viemann, Dorothee

AU - Prinz, Immo

PY - 2020/8/4

Y1 - 2020/8/4

N2 - 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. These were 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.

AB - 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. These were 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.

KW - Africa South of the Sahara

KW - Bacteria/immunology

KW - Child

KW - Child, Preschool

KW - Europe

KW - Gene Rearrangement, T-Lymphocyte/genetics

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Longitudinal Studies

KW - Receptors, Antigen, T-Cell, gamma-delta/genetics

KW - T-Lymphocyte Subsets/immunology

U2 - 10.1073/pnas.1922588117

DO - 10.1073/pnas.1922588117

M3 - SCORING: Journal article

C2 - 32690687

VL - 117

SP - 18649

EP - 18660

JO - P NATL ACAD SCI USA

JF - P NATL ACAD SCI USA

SN - 0027-8424

IS - 31

ER -