ThymoSpheres culture: A model to study human polyclonal unconventional T cells.

Autor:	Billiet L; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium., Jansen H; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium., Pille M; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium., Boehme L; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium., Sanchez Sanchez G; Department of Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles (ULB), Brussels, Belgium.; Institute for Medical Immunology, Université Libre de Bruxelles (ULB), Brussels, Belgium.; ULB Center for Research in Immunology (U-CRI), Université Libre de Bruxelles (ULB), Brussels, Belgium.; WELBIO Department, WEL Research Institute, Wavre, Belgium., De Cock L; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.; Cancer Research Institute Ghent (CRIG), Ghent, Belgium., Goetgeluk G; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.; Cancer Research Institute Ghent (CRIG), Ghent, Belgium., Pascal E; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.; Cancer Research Institute Ghent (CRIG), Ghent, Belgium., De Munter S; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.; Cancer Research Institute Ghent (CRIG), Ghent, Belgium., Deseins L; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.; Cancer Research Institute Ghent (CRIG), Ghent, Belgium.; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium., Ingels J; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.; Cancer Research Institute Ghent (CRIG), Ghent, Belgium.; GMP Unit CellGenTherapies, Ghent University Hospital, Ghent, Belgium., Michiels T; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.; Cancer Research Institute Ghent (CRIG), Ghent, Belgium., De Vos R; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.; Cancer Research Institute Ghent (CRIG), Ghent, Belgium.; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium., Zolfaghari A; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.; Cancer Research Institute Ghent (CRIG), Ghent, Belgium., Vandamme N; VIB Single Cell Core, VIB, Ghent, Belgium.; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium., Roels J; VIB Single Cell Core, VIB, Ghent, Belgium.; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium., Kerre T; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.; Cancer Research Institute Ghent (CRIG), Ghent, Belgium.; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium., Dmitriev RI; Tissue Engineering and Biomaterials Group, Department of Human Structure and Repair, Ghent University, Ghent, Belgium., Taghon T; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.; Cancer Research Institute Ghent (CRIG), Ghent, Belgium., Vermijlen D; Department of Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles (ULB), Brussels, Belgium.; Institute for Medical Immunology, Université Libre de Bruxelles (ULB), Brussels, Belgium.; ULB Center for Research in Immunology (U-CRI), Université Libre de Bruxelles (ULB), Brussels, Belgium.; WELBIO Department, WEL Research Institute, Wavre, Belgium., Vandekerckhove B; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.; Cancer Research Institute Ghent (CRIG), Ghent, Belgium.; GMP Unit CellGenTherapies, Ghent University Hospital, Ghent, Belgium.
Jazyk:	angličtina
Zdroj:	European journal of immunology [Eur J Immunol] 2024 Sep 09, pp. e2451265. Date of Electronic Publication: 2024 Sep 09.
DOI:	10.1002/eji.202451265
Abstrakt:	In vitro cultures remain crucial for studying the fundamental mechanisms of human T-cell development. Here, we introduce a novel in vitro cultivation system based on ThymoSpheres (TS): dense spheroids consisting of DLL4-expressing stromal cells and human hematopoietic precursor cells, in the absence of thymic epithelial cells. These spheroids are subsequently cultured at the air-liquid interphase. TS generate large numbers of mature T cells, are easy to manipulate, scalable, and can be repeatably sampled to monitor T-cell differentiation. The mature T cells generated from primary human hematopoietic precursor cells were extensively characterized using single-cell RNA and combined T-cell receptor (TCR) sequencing. These predominantly CD8α T cells exhibit transcriptional and TCR CDR3 characteristics similar to the recently described human polyclonal αβ unconventional T cell (UTC) lineage. This includes the expression of hallmark genes associated with agonist selection, such as IKZF2 (Helios), and the expression of various natural killer receptors. The TCR repertoire of these UTCs is polyclonal and enriched for CDR3-associated autoreactive features and early rearrangements of the TCR-α chain. In conclusion, TS cultures offer an intriguing platform to study the development of this human polyclonal UTC lineage and its inducing selection mechanisms. (© 2024 The Author(s). European Journal of Immunology published by Wiley‐VCH GmbH.)
Databáze:	MEDLINE
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