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


Journal

The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R

Informations de publication

Date de publication:
05 06 2023
Historique:
received: 30 05 2022
revised: 22 12 2022
accepted: 27 02 2023
entrez: 20 3 2023
pubmed: 21 3 2023
medline: 23 3 2023
Statut: ppublish

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.

Identifiants

pubmed: 36939517
pii: 213952
doi: 10.1084/jem.20220942
pmc: PMC10037106
pii:
doi:

Substances chimiques

Receptors, Antigen, T-Cell, alpha-beta 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2023 Billiet et al.

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Auteurs

Lore Billiet (L)

Department of Diagnostic Sciences, Ghent University , Ghent, Belgium.

Laurenz De Cock (L)

Department of Biomolecular Medicine, Ghent University , Ghent, Belgium.
Cancer Research Institute Ghent , Ghent, Belgium.

Guillem Sanchez Sanchez (G)

Department of Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles , Brussels, Belgium.
Institute for Medical Immunology, Université Libre de Bruxelles , Brussels, Belgium.
Université Libre de Bruxelles Center for Research in Immunology, Université Libre de Bruxelles , Brussels, Belgium.
WELBIO Department, WEL Research Institute, Wavre, Belgium.

Rupert L Mayer (RL)

Department of Biomolecular Medicine, Ghent University , Ghent, Belgium.
VIB-UGent Center for Medical Biotechnology, VIB , Ghent, Belgium.
VIB Proteomics Core, VIB , Ghent, Belgium.

Glenn Goetgeluk (G)

Department of Diagnostic Sciences, Ghent University , Ghent, Belgium.
Cancer Research Institute Ghent , Ghent, Belgium.

Stijn De Munter (S)

Department of Diagnostic Sciences, Ghent University , Ghent, Belgium.
Cancer Research Institute Ghent , Ghent, Belgium.

Melissa Pille (M)

Department of Diagnostic Sciences, Ghent University , Ghent, Belgium.

Joline Ingels (J)

Department of Diagnostic Sciences, Ghent University , Ghent, Belgium.
Cancer Research Institute Ghent , Ghent, Belgium.

Hanne Jansen (H)

Department of Diagnostic Sciences, Ghent University , Ghent, Belgium.

Karin Weening (K)

Department of Diagnostic Sciences, Ghent University , Ghent, Belgium.

Eva Pascal (E)

Department of Diagnostic Sciences, Ghent University , Ghent, Belgium.
Cancer Research Institute Ghent , Ghent, Belgium.

Killian Raes (K)

Department of Diagnostic Sciences, Ghent University , Ghent, Belgium.

Sarah Bonte (S)

Cancer Research Institute Ghent , Ghent, Belgium.
Department of Internal Medicine and Pediatrics, Ghent University , Ghent, Belgium.
Data Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation Research , Ghent, Belgium.

Tessa Kerre (T)

Department of Diagnostic Sciences, Ghent University , Ghent, Belgium.
Cancer Research Institute Ghent , Ghent, Belgium.
Department of Internal Medicine and Pediatrics, Ghent University , Ghent, Belgium.

Niels Vandamme (N)

VIB Single Cell Core, VIB , Ghent, Belgium.
Data Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation Research , Ghent, Belgium.

Ruth Seurinck (R)

Data Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation Research , Ghent, Belgium.

Jana Roels (J)

VIB Single Cell Core, VIB , Ghent, Belgium.
Data Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation Research , Ghent, Belgium.

Marieke Lavaert (M)

Department of Diagnostic Sciences, Ghent University , Ghent, Belgium.

Filip Van Nieuwerburgh (F)

Cancer Research Institute Ghent , Ghent, Belgium.
Department of Pharmaceutics, Ghent University , Ghent, Belgium.

Georges Leclercq (G)

Department of Diagnostic Sciences, Ghent University , Ghent, Belgium.
Cancer Research Institute Ghent , Ghent, Belgium.

Tom Taghon (T)

Department of Diagnostic Sciences, Ghent University , Ghent, Belgium.
Cancer Research Institute Ghent , Ghent, Belgium.

Francis Impens (F)

Department of Biomolecular Medicine, Ghent University , Ghent, Belgium.
VIB-UGent Center for Medical Biotechnology, VIB , Ghent, Belgium.
VIB Proteomics Core, VIB , Ghent, Belgium.

Björn Menten (B)

Department of Biomolecular Medicine, Ghent University , Ghent, Belgium.

David Vermijlen (D)

Department of Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles , Brussels, Belgium.
Institute for Medical Immunology, Université Libre de Bruxelles , Brussels, Belgium.
Université Libre de Bruxelles Center for Research in Immunology, Université Libre de Bruxelles , Brussels, Belgium.
WELBIO Department, WEL Research Institute, Wavre, Belgium.

Bart Vandekerckhove (B)

Department of Diagnostic Sciences, Ghent University , Ghent, Belgium.
Cancer Research Institute Ghent , Ghent, Belgium.

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