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, Jahrgang 117, Nr. 31, 04.08.2020, S. 18649-18660.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -