Identification of distinct functional thymic programming of fetal and pediatric human γδ thymocytes via single-cell analysis

Guillem Sanchez Sanchez, Maria Papadopoulou, Abdulkader Azouz, Yohannes Tafesse, Archita Mishra, Jerry K.Y. Chan, Yiping Fan, Isoline Verdebout, Silvana Porco, Frédérick Libert, Florent Ginhoux, Bart Vandekerckhove, Stanislas Goriely, David Vermijlen

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Developmental thymic waves of innate-like and adaptive-like γδ T cells have been described, but the current understanding of γδ T cell development is mainly limited to mouse models. Here, we combine single cell (sc) RNA gene expression and sc γδ T cell receptor (TCR) sequencing on fetal and pediatric γδ thymocytes in order to understand the ontogeny of human γδ T cells. Mature fetal γδ thymocytes (both the Vγ9Vδ2 and nonVγ9Vδ2 subsets) are committed to either a type 1, a type 3 or a type 2-like effector fate displaying a wave-like pattern depending on gestation age, and are enriched for public CDR3 features upon maturation. Strikingly, these effector modules express different CDR3 sequences and follow distinct developmental trajectories. In contrast, the pediatric thymus generates only a small effector subset that is highly biased towards Vγ9Vδ2 TCR usage and shows a mixed type 1/type 3 effector profile. Thus, our combined dataset of gene expression and detailed TCR information at the single-cell level identifies distinct functional thymic programming of γδ T cell immunity in human.

Original languageEnglish
Article number5842
JournalNature Communications
Volume13
Issue number1
DOIs
Publication statusPublished - Dec 2022

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