Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/23147
Title: GPA33: A Marker to Identify Stable Human Regulatory T Cells.
Authors: Opstelten, Rianne;de Kivit, Sander;Slot, Manon C;van den Biggelaar, Maartje;Iwaszkiewicz-Grześ, Dorota;Gliwiński, Mateusz;Scott, Andrew M;Blom, Bianca;Trzonkowski, Piotr;Borst, Jannie;Cuadrado, Eloy;Amsen, Derk
Affiliation: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, the Netherlands
La Trobe School of Cancer Medicine, La Trobe University, Melbourne, Victoria, VIC 3086 Australia
Division of Tumor Biology and Immunology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, the Netherlands
Tumor Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, the Netherlands
Department of Molecular and Cellular Homeostasis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, the Netherlands
Department of Medical Immunology, Medical University of Gdańsk, 80-210 Gdańsk, Poland
Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
Department of Medical Immunology, Medical University of Gdańsk, 80-210 Gdańsk, Poland
Division of Tumor Biology and Immunology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, the Netherlands
Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, the Netherlands
Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, the Netherlands;.
Issue Date: 4-May-2020
EDate: 2020-05-04
Citation: Journal of immunology (Baltimore, Md. : 1950) 2020; online first: 4 May
Abstract: FOXP3-expressing regulatory T (Treg) cells safeguard immunological tolerance. Treg cells can be generated during thymic development (called thymic Treg [tTreg] cells) or derived from mature conventional CD4+ T cells that underwent TGF-β-mediated conversion in the periphery (called peripheral Treg [pTreg] cells). Murine studies have shown that tTreg cells exhibit strong lineage fidelity, whereas pTreg cells can revert into conventional CD4+ T cells. Their stronger lineage commitment makes tTreg cells the safest cells to use in adoptive cell therapy, increasingly used to treat autoimmune and inflammatory disorders. Markers to distinguish human tTreg cells from pTreg cells have, however, not been found. Based on combined proteomic and transcriptomic approaches, we report that the Ig superfamily protein GPA33 is expressed on a subset of human Treg cells. GPA33 is acquired late during tTreg cell development but is not expressed on TGF-β-induced Treg cells. GPA33 identifies Treg cells in human blood that lack the ability to produce effector cytokines (IL-2, IFN-γ, IL-17), regardless of differentiation stage. GPA33high Treg cells universally express the transcription factor Helios that preferentially marks tTreg cells and can robustly and stably be expanded in vitro even without rapamycin. Expanded GPA33high Treg cells are suppressive, unable to produce proinflammatory cytokines, and exhibit the epigenetic modifications of the FOXP3 gene enhancer CNS2, necessary for indelible expression of this critical transcription factor. Our findings thus suggest that GPA33 identifies human tTreg cells and provide a strategy to isolate such cells for safer and more efficacious adoptive cell therapy.
URI: http://ahro.austin.org.au/austinjspui/handle/1/23147
DOI: 10.4049/jimmunol.1901250
ORCID: 0000-0003-0148-7802
0000-0001-9376-3231
0000-0001-5287-5210
0000-0002-6656-295X
PubMed URL: 32366581
Type: Journal Article
Appears in Collections:Journal articles

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