TCR sequencing reveals the distinct development of fetal and adult human Vγ9Vδ2 T cells

Maria Papadopoulou, Paola Tieppo, Naomi McGovern, Françoise Gosselin, Jerry K.Y. Chan, Glenn Goetgeluk, Nicolas Dauby, Alexandra Cogan, Catherine Donner, Florent Ginhoux, Bart Vandekerckhove, David Vermijlen

Résultats de recherche: Contribution à un journalArticleRevue par des pairs

50 Citations (Scopus)

Résumé

Phosphoantigen-reactive Vγ9Vδ2 T cells represent the main innate human gd T cell subset and dominate the fetal and adult peripheral blood gd T cell repertoire. It has been hypothesized that adult blood Vγ9Vδ2 T cells find their origin in the fetus like it is established for mouse innate gd T cells. To address this issue, we analyzed the CDR3 of the TCR of human blood and thymic Vγ9Vδ2 T cells from fetal until adult life. We first identified key differences in the CDR3 repertoire of fetal and adult blood Vγ9Vδ2 T cells, including in CDR3 features important for phosphoantigen reactivity. Next, we showed that most of these key adult CDR3 features were already present in the postnatal thymus and were further enhanced upon selection in vitro by the microbial-derived phosphoantigen (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate. Finally, we demonstrated that the generation of a fetal-type or adult-type Vγ9Vδ2 CDR3 repertoire is determined by the fetal and postnatal nature of the hematopoietic stem and precursor cell. Thus, our data indicate that fetal blood Vγ9Vδ2 T cells find their origin in the fetal thymus whereas adult blood Vγ9Vδ2 T cells are generated to a large degree independently after birth.

langue originaleAnglais
Pages (de - à)1468-1479
Nombre de pages12
journalJournal of Immunology
Volume203
Numéro de publication6
Les DOIs
étatPublié - 15 sept. 2019
Modification externeOui

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