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Single-cell profiling identifies a novel human polyclonal unconventional T cell lineage

par Billiet, Lore;De Cock, Laurenz;Sánchez Sánchez, Guillem ;Mayer, Rupert L.;Goetgeluk, Glenn;De Munter, Stijn;Pille, Melissa;Ingels, Joline;Jansen, Hanne;Weening, Karin;Pascal, Eva;Raes, Killian;Bonte, Sarah;Kerre, Tessa;Vandamme, Niels;Seurinck, Ruth;Roels, Jolien;Lavaert, Marieke;Van Nieuwerburgh, Filip;Leclercq, Georges ;Taghon, Tom;Impens, Francis;Menten, Björn;Vermijlen, David ;Vandekerckhove, Bart
Référence The Journal of experimental medicine, 220, 6
Publication Publié, 2023-06-05

Article révisé par les pairs

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Résumé :

In the human thymus, a CD10+ PD-1+ TCRαβ+ differentiation pathway diverges from the conventional single positive T cell lineages at the early double-positive stage. Here, we identify the progeny of this unconventional lineage in antigen-inexperienced blood. These unconventional T cells (UTCs) in thymus and blood share a transcriptomic profile, characterized by hallmark transcription factors (i.e., ZNF683 and IKZF2), and a polyclonal TCR repertoire with autoreactive features, exhibiting a bias toward early TCRα chain rearrangements. Single-cell RNA sequencing confirms a common developmental trajectory between the thymic and blood UTCs and clearly delineates this unconventional lineage in blood. Besides MME+ recent thymic emigrants, effector-like clusters are identified in this heterogeneous lineage. Expression of Helios and KIR and a decreased CD8β expression are characteristics of this lineage. This UTC lineage could be identified in adult blood and intestinal tissues. In summary, our data provide a comprehensive characterization of the polyclonal unconventional lineage in antigen-inexperienced blood and identify the adult progeny.