Publication: Extracellular adenosine reversibly inhibits the activation of human regulatory T cells and negatively influences the achievement of the operational tolerance in liver transplantation
Authors
Baroja-Mazo, Alberto ; Revilla-Nuin, Beatriz ; Bejar, Africa de ; Martinez-Alarcón, Laura ; Herrero, José I. ; El-Tayeb, Ali ; Müller, Christa E. ; Aparicio, Pedro ; Pons Miñano, José Antonio ; Pelegrín Vivancos, Pablo
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Publisher
Wiley
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DOI
https://doi.org/10.1111/ajt.15023
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info:eu-repo/semantics/article
Description
© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons. This document is the Published,version of a Published Work that appeared in final form in American Journal of Transplantation. To access the final edited and published work see https://doi.org/10.1111/ajt.15023
Abstract
The artificial induction of tolerance in transplantation is gaining strength. In mice, a differential role of extracellular adenosine (eADO) for regulatory and effector T cells (Tregs and Teffs, respectively) has been proposed: inhibiting Teffs and inducing Tregs. The aim of this study was to analyze the action of extracellular nucleotides in human T cells and, moreover, to examine the influence of CD39 and CD73 ectonucleotidases and subsequent adenosine signaling through adenosine 2 receptor (A2R) in the induction of clinical tolerance after liver transplant. The action of extracellular nucleotides
in human T cells was analyzed by in vitro experiments with isolated T cells. Additionally, 17 liver transplant patients were enrolled in an immunosuppression withdrawal trial, and the differences in the CD39‐CD73‐A2R axis were compared between tolerant and nontolerant patients. In contrast to the mice, the activation of human Tregs was inhibited similarly to Teffs in the presence of eADO. Moreover, the expression of the
enzyme responsible for the degradation of ADO, adenosine deaminase, was higher in tolerant patients with respect to the nontolerant group along the immunosuppression withdrawal. Our data support the idea that eADO signaling and its degradation may play a role in the complex system of regulation of liver transplant tolerance.
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Basic (laboratory) research/science , Cellular biology , Immune regulation , Immunosuppression/immune modulation , Immunosuppressive regimens ‐ minimization/withdrawal , Liver transplantation/hepatology , SIgnaling/signaling pathways , T cell biology , Tolerance: Clinical , Translational research/science
Citation
Am J Transplant 2019 19:48–61.
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