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Human Regulatory T Cell Suppressive Function Is Independent of Apoptosis Induction in Activated Effector T Cells

BACKGROUND: CD4(+)CD25(+)FOXP3(+) Regulatory T cells (Treg) play a central role in the immune balance to prevent autoimmune disease. One outstanding question is how Tregs suppress effector immune responses in human. Experiments in mice demonstrated that Treg restrict effector T cell (Teff) responses...

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Autores principales: Vercoulen, Yvonne, Wehrens, Ellen J., van Teijlingen, Nienke H., de Jager, Wilco, Beekman, Jeffrey M., Prakken, Berent J.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2746309/
https://www.ncbi.nlm.nih.gov/pubmed/19779623
http://dx.doi.org/10.1371/journal.pone.0007183
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author Vercoulen, Yvonne
Wehrens, Ellen J.
van Teijlingen, Nienke H.
de Jager, Wilco
Beekman, Jeffrey M.
Prakken, Berent J.
author_facet Vercoulen, Yvonne
Wehrens, Ellen J.
van Teijlingen, Nienke H.
de Jager, Wilco
Beekman, Jeffrey M.
Prakken, Berent J.
author_sort Vercoulen, Yvonne
collection PubMed
description BACKGROUND: CD4(+)CD25(+)FOXP3(+) Regulatory T cells (Treg) play a central role in the immune balance to prevent autoimmune disease. One outstanding question is how Tregs suppress effector immune responses in human. Experiments in mice demonstrated that Treg restrict effector T cell (Teff) responses by deprivation of the growth factor IL-2 through Treg consumption, resulting in apoptosis of Teff. PRINCIPAL FINDINGS: In this study we investigated the relevance of Teff apoptosis induction to human Treg function. To this end, we studied naturally occurring Treg (nTreg) from peripheral blood of healthy donors, and, to investigate Treg function in inflammation in vivo, Treg from synovial fluid of Juvenile Idiopathic Arthritis (JIA) patients (SF-Treg). Both nTreg and SF-Treg suppress Teff proliferation and cytokine production efficiently as predicted. However, in contrast with murine Treg, neither nTreg nor SF-Treg induce apoptosis in Teff. Furthermore, exogenously supplied IL-2 and IL-7 reverse suppression, but do not influence apoptosis of Teff. SIGNIFICANCE: Our functional data here support that Treg are excellent clinical targets to counteract autoimmune diseases. For optimal functional outcome in human clinical trials, future work should focus on the ability of Treg to suppress proliferation and cytokine production of Teff, rather than induction of Teff apoptosis.
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spelling pubmed-27463092009-09-25 Human Regulatory T Cell Suppressive Function Is Independent of Apoptosis Induction in Activated Effector T Cells Vercoulen, Yvonne Wehrens, Ellen J. van Teijlingen, Nienke H. de Jager, Wilco Beekman, Jeffrey M. Prakken, Berent J. PLoS One Research Article BACKGROUND: CD4(+)CD25(+)FOXP3(+) Regulatory T cells (Treg) play a central role in the immune balance to prevent autoimmune disease. One outstanding question is how Tregs suppress effector immune responses in human. Experiments in mice demonstrated that Treg restrict effector T cell (Teff) responses by deprivation of the growth factor IL-2 through Treg consumption, resulting in apoptosis of Teff. PRINCIPAL FINDINGS: In this study we investigated the relevance of Teff apoptosis induction to human Treg function. To this end, we studied naturally occurring Treg (nTreg) from peripheral blood of healthy donors, and, to investigate Treg function in inflammation in vivo, Treg from synovial fluid of Juvenile Idiopathic Arthritis (JIA) patients (SF-Treg). Both nTreg and SF-Treg suppress Teff proliferation and cytokine production efficiently as predicted. However, in contrast with murine Treg, neither nTreg nor SF-Treg induce apoptosis in Teff. Furthermore, exogenously supplied IL-2 and IL-7 reverse suppression, but do not influence apoptosis of Teff. SIGNIFICANCE: Our functional data here support that Treg are excellent clinical targets to counteract autoimmune diseases. For optimal functional outcome in human clinical trials, future work should focus on the ability of Treg to suppress proliferation and cytokine production of Teff, rather than induction of Teff apoptosis. Public Library of Science 2009-09-25 /pmc/articles/PMC2746309/ /pubmed/19779623 http://dx.doi.org/10.1371/journal.pone.0007183 Text en Vercoulen et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Vercoulen, Yvonne
Wehrens, Ellen J.
van Teijlingen, Nienke H.
de Jager, Wilco
Beekman, Jeffrey M.
Prakken, Berent J.
Human Regulatory T Cell Suppressive Function Is Independent of Apoptosis Induction in Activated Effector T Cells
title Human Regulatory T Cell Suppressive Function Is Independent of Apoptosis Induction in Activated Effector T Cells
title_full Human Regulatory T Cell Suppressive Function Is Independent of Apoptosis Induction in Activated Effector T Cells
title_fullStr Human Regulatory T Cell Suppressive Function Is Independent of Apoptosis Induction in Activated Effector T Cells
title_full_unstemmed Human Regulatory T Cell Suppressive Function Is Independent of Apoptosis Induction in Activated Effector T Cells
title_short Human Regulatory T Cell Suppressive Function Is Independent of Apoptosis Induction in Activated Effector T Cells
title_sort human regulatory t cell suppressive function is independent of apoptosis induction in activated effector t cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2746309/
https://www.ncbi.nlm.nih.gov/pubmed/19779623
http://dx.doi.org/10.1371/journal.pone.0007183
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