Reduced Numbers and Impaired Function of Regulatory T Cells in Peripheral Blood of Ischemic Stroke Patients

Background and Purpose. Regulatory T cells (Tregs) have been suggested to modulate stroke-induced immune responses. However, analyses of Tregs in patients and in experimental stroke have yielded contradictory findings. We performed the current study to assess the regulation and function of Tregs in...

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Main Authors: Johanna Ruhnau, Juliane Schulze, Bettina von Sarnowski, Marie Heinrich, Sönke Langner, Christian Pötschke, Anika Wilden, Christof Kessler, Barbara M. Bröker, Antje Vogelgesang, Alexander Dressel
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2016/2974605
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author Johanna Ruhnau
Juliane Schulze
Bettina von Sarnowski
Marie Heinrich
Sönke Langner
Christian Pötschke
Anika Wilden
Christof Kessler
Barbara M. Bröker
Antje Vogelgesang
Alexander Dressel
author_facet Johanna Ruhnau
Juliane Schulze
Bettina von Sarnowski
Marie Heinrich
Sönke Langner
Christian Pötschke
Anika Wilden
Christof Kessler
Barbara M. Bröker
Antje Vogelgesang
Alexander Dressel
author_sort Johanna Ruhnau
collection DOAJ
description Background and Purpose. Regulatory T cells (Tregs) have been suggested to modulate stroke-induced immune responses. However, analyses of Tregs in patients and in experimental stroke have yielded contradictory findings. We performed the current study to assess the regulation and function of Tregs in peripheral blood of stroke patients. Age dependent expression of CD39 on Tregs was quantified in mice and men. Methods. Total FoxP3+ Tregs and CD39+FoxP3+ Tregs were quantified by flow cytometry in controls and stroke patients on admission and on days 1, 3, 5, and 7 thereafter. Treg function was assessed by quantifying the inhibition of activation-induced expression of CD69 and CD154 on T effector cells (Teffs). Results. Total Tregs accounted for 5.0% of CD4+ T cells in controls and <2.8% in stroke patients on admission. They remained below control values until day 7. CD39+ Tregs were most strongly reduced in stroke patients. On day 3 the Treg-mediated inhibition of CD154 upregulation on CD4+ Teff was impaired in stroke patients. CD39 expression on Treg increased with age in peripheral blood of mice and men. Conclusion. We demonstrate a loss of active FoxP3+CD39+ Tregs from stroke patient’s peripheral blood. The suppressive Treg function of remaining Tregs is impaired after stroke.
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spelling doaj-art-daa95971e6a841688250db4d159c72be2025-02-03T06:13:21ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/29746052974605Reduced Numbers and Impaired Function of Regulatory T Cells in Peripheral Blood of Ischemic Stroke PatientsJohanna Ruhnau0Juliane Schulze1Bettina von Sarnowski2Marie Heinrich3Sönke Langner4Christian Pötschke5Anika Wilden6Christof Kessler7Barbara M. Bröker8Antje Vogelgesang9Alexander Dressel10Department of Neurology, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment of Neurology, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment of Neurology, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment of Neurology, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment of Immunology, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment of Neurology, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment of Neurology, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment of Immunology, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment of Neurology, University Medicine Greifswald, 17475 Greifswald, GermanyDepartment of Neurology, University Medicine Greifswald, 17475 Greifswald, GermanyBackground and Purpose. Regulatory T cells (Tregs) have been suggested to modulate stroke-induced immune responses. However, analyses of Tregs in patients and in experimental stroke have yielded contradictory findings. We performed the current study to assess the regulation and function of Tregs in peripheral blood of stroke patients. Age dependent expression of CD39 on Tregs was quantified in mice and men. Methods. Total FoxP3+ Tregs and CD39+FoxP3+ Tregs were quantified by flow cytometry in controls and stroke patients on admission and on days 1, 3, 5, and 7 thereafter. Treg function was assessed by quantifying the inhibition of activation-induced expression of CD69 and CD154 on T effector cells (Teffs). Results. Total Tregs accounted for 5.0% of CD4+ T cells in controls and <2.8% in stroke patients on admission. They remained below control values until day 7. CD39+ Tregs were most strongly reduced in stroke patients. On day 3 the Treg-mediated inhibition of CD154 upregulation on CD4+ Teff was impaired in stroke patients. CD39 expression on Treg increased with age in peripheral blood of mice and men. Conclusion. We demonstrate a loss of active FoxP3+CD39+ Tregs from stroke patient’s peripheral blood. The suppressive Treg function of remaining Tregs is impaired after stroke.http://dx.doi.org/10.1155/2016/2974605
spellingShingle Johanna Ruhnau
Juliane Schulze
Bettina von Sarnowski
Marie Heinrich
Sönke Langner
Christian Pötschke
Anika Wilden
Christof Kessler
Barbara M. Bröker
Antje Vogelgesang
Alexander Dressel
Reduced Numbers and Impaired Function of Regulatory T Cells in Peripheral Blood of Ischemic Stroke Patients
Mediators of Inflammation
title Reduced Numbers and Impaired Function of Regulatory T Cells in Peripheral Blood of Ischemic Stroke Patients
title_full Reduced Numbers and Impaired Function of Regulatory T Cells in Peripheral Blood of Ischemic Stroke Patients
title_fullStr Reduced Numbers and Impaired Function of Regulatory T Cells in Peripheral Blood of Ischemic Stroke Patients
title_full_unstemmed Reduced Numbers and Impaired Function of Regulatory T Cells in Peripheral Blood of Ischemic Stroke Patients
title_short Reduced Numbers and Impaired Function of Regulatory T Cells in Peripheral Blood of Ischemic Stroke Patients
title_sort reduced numbers and impaired function of regulatory t cells in peripheral blood of ischemic stroke patients
url http://dx.doi.org/10.1155/2016/2974605
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