Microbial exposure drives polyclonal expansion of innate ?? 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 ?? 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 ?? T cell repertoires are shaped by microbial exposure after birth, we monitored the ?-chain (TRG) and ?-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?9 and V?2 chains with low junctional diversity and usage of non-TRDJ1 gene segments, reminiscent of early ontogenetic subsets of ?? T cells. Further profiling revealed that these innate, public V?9V?2⁺ T cells underwent an immediate TCR-driven polyclonal proliferation within the first 4 wk of life. In contrast, ?? T cells using V?1⁺ and V?3⁺ TRD rearrangements did not significantly expand after birth. However, different environmental cues may lead to the observed increase of V?1⁺ and V?3⁺ TRD sequences in the majority of African children. In summary, we show how dynamic ?? TCR repertoires develop directly after birth and present important differences among ?? T cell subsets.

SUBMITTER: Ravens S 

PROVIDER: S-EPMC7414158 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature