CD73-mediated adenosine production by CD8 T cell-derived extracellular vesicles constitutes an intrinsic mechanism of immune suppression

Enja Schneider, Riekje Winzer (), Anne Rissiek, Isabell Ricklefs, Catherine Meyer-Schwesinger, Franz L. Ricklefs, Andreas Bauche, Jochen Behrends, Rudolph Reimer, Santra Brenna, Hauke Wasielewski, Melchior Lauten, Björn Rissiek, Berta Puig, Filippo Cortesi, Tim Magnus, Ralf Fliegert, Christa E. Müller, Nicola Gagliani and Eva Tolosa ()
Additional contact information
Enja Schneider: University Medical Center Hamburg-Eppendorf
Riekje Winzer: University Medical Center Hamburg-Eppendorf
Anne Rissiek: University Medical Center Hamburg-Eppendorf
Isabell Ricklefs: University Medical Center Schleswig-Holstein
Catherine Meyer-Schwesinger: University Medical Center Hamburg-Eppendorf
Franz L. Ricklefs: University Medical Center Hamburg-Eppendorf
Andreas Bauche: University Medical Center Hamburg-Eppendorf
Jochen Behrends: Core Facility Fluorescence Cytometry, Research Center Borstel
Rudolph Reimer: Technology Platform Microscopy and Image Analysis, Heinrich Pette Institute/Leibniz Institute for Experimental Virology
Santra Brenna: University Medical Center Hamburg-Eppendorf
Hauke Wasielewski: University Medical Center Hamburg-Eppendorf
Melchior Lauten: University of Lübeck
Björn Rissiek: University Medical Center Hamburg-Eppendorf
Berta Puig: University Medical Center Hamburg-Eppendorf
Filippo Cortesi: University Medical Center Hamburg-Eppendorf
Tim Magnus: University Medical Center Hamburg-Eppendorf
Ralf Fliegert: University Medical Center Hamburg-Eppendorf
Christa E. Müller: University of Bonn
Nicola Gagliani: University Medical Center Hamburg-Eppendorf
Eva Tolosa: University Medical Center Hamburg-Eppendorf

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Immune cells at sites of inflammation are continuously activated by local antigens and cytokines, and regulatory mechanisms must be enacted to control inflammation. The stepwise hydrolysis of extracellular ATP by ectonucleotidases CD39 and CD73 generates adenosine, a potent immune suppressor. Here we report that human effector CD8 T cells contribute to adenosine production by releasing CD73-containing extracellular vesicles upon activation. These extracellular vesicles have AMPase activity, and the resulting adenosine mediates immune suppression independently of regulatory T cells. In addition, we show that extracellular vesicles isolated from the synovial fluid of patients with juvenile idiopathic arthritis contribute to T cell suppression in a CD73-dependent manner. Our results suggest that the generation of adenosine upon T cell activation is an intrinsic mechanism of human effector T cells that complements regulatory T cell-mediated suppression in the inflamed tissue. Finally, our data underscore the role of immune cell-derived extracellular vesicles in the control of immune responses.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26134-w

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DOI: 10.1038/s41467-021-26134-w

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