Basiliximab impairs regulatory T cell (TREG) function and could affect the short-term graft acceptance in children with heart transplantation

Abstract CD25, the alpha chain of the IL-2 receptor, is expressed on activated effector T cells that mediate immune graft damage. Induction immunosuppression is commonly used in solid organ transplantation and can include antibodies blocking CD25. However, regulatory T cells (Tregs) also rely on CD2...

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Autores principales: Jacobo López-Abente, Marta Martínez-Bonet, Esther Bernaldo-de-Quirós, Manuela Camino, Nuria Gil, Esther Panadero, Juan Miguel Gil-Jaurena, Maribel Clemente, Simon Urschel, Lori West, Marjorie Pion, Rafael Correa-Rocha
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spelling oai:doaj.org-article:4c11fa0c07a241ce8f6dbe296a31b1802021-12-02T14:12:09ZBasiliximab impairs regulatory T cell (TREG) function and could affect the short-term graft acceptance in children with heart transplantation10.1038/s41598-020-80567-92045-2322https://doaj.org/article/4c11fa0c07a241ce8f6dbe296a31b1802021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80567-9https://doaj.org/toc/2045-2322Abstract CD25, the alpha chain of the IL-2 receptor, is expressed on activated effector T cells that mediate immune graft damage. Induction immunosuppression is commonly used in solid organ transplantation and can include antibodies blocking CD25. However, regulatory T cells (Tregs) also rely on CD25 for their proliferation, survival, and regulatory function. Therefore, CD25-blockade may compromise Treg protective role against rejection. We analysed in vitro the effect of basiliximab (BXM) on the viability, phenotype, proliferation and cytokine production of Treg cells. We also evaluated in vivo the effect of BXM on Treg in thymectomized heart transplant children receiving BXM in comparison to patients not receiving induction therapy. Our results show that BXM reduces Treg counts and function in vitro by affecting their proliferation, Foxp3 expression, and IL-10 secretion capacity. In pediatric heart-transplant patients, we observed decreased Treg counts and a diminished Treg/Teff ratio in BXM-treated patients up to 6-month after treatment, recovering baseline values at the end of the 12-month follow up period. These results reveal that the use of BXM could produce detrimental effects on Tregs, and support the evidence suggesting that BXM induction could impair the protective role of Tregs in the period of highest incidence of acute graft rejection.Jacobo López-AbenteMarta Martínez-BonetEsther Bernaldo-de-QuirósManuela CaminoNuria GilEsther PanaderoJuan Miguel Gil-JaurenaMaribel ClementeSimon UrschelLori WestMarjorie PionRafael Correa-RochaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Jacobo López-Abente
Marta Martínez-Bonet
Esther Bernaldo-de-Quirós
Manuela Camino
Nuria Gil
Esther Panadero
Juan Miguel Gil-Jaurena
Maribel Clemente
Simon Urschel
Lori West
Marjorie Pion
Rafael Correa-Rocha
Basiliximab impairs regulatory T cell (TREG) function and could affect the short-term graft acceptance in children with heart transplantation
description Abstract CD25, the alpha chain of the IL-2 receptor, is expressed on activated effector T cells that mediate immune graft damage. Induction immunosuppression is commonly used in solid organ transplantation and can include antibodies blocking CD25. However, regulatory T cells (Tregs) also rely on CD25 for their proliferation, survival, and regulatory function. Therefore, CD25-blockade may compromise Treg protective role against rejection. We analysed in vitro the effect of basiliximab (BXM) on the viability, phenotype, proliferation and cytokine production of Treg cells. We also evaluated in vivo the effect of BXM on Treg in thymectomized heart transplant children receiving BXM in comparison to patients not receiving induction therapy. Our results show that BXM reduces Treg counts and function in vitro by affecting their proliferation, Foxp3 expression, and IL-10 secretion capacity. In pediatric heart-transplant patients, we observed decreased Treg counts and a diminished Treg/Teff ratio in BXM-treated patients up to 6-month after treatment, recovering baseline values at the end of the 12-month follow up period. These results reveal that the use of BXM could produce detrimental effects on Tregs, and support the evidence suggesting that BXM induction could impair the protective role of Tregs in the period of highest incidence of acute graft rejection.
format article
author Jacobo López-Abente
Marta Martínez-Bonet
Esther Bernaldo-de-Quirós
Manuela Camino
Nuria Gil
Esther Panadero
Juan Miguel Gil-Jaurena
Maribel Clemente
Simon Urschel
Lori West
Marjorie Pion
Rafael Correa-Rocha
author_facet Jacobo López-Abente
Marta Martínez-Bonet
Esther Bernaldo-de-Quirós
Manuela Camino
Nuria Gil
Esther Panadero
Juan Miguel Gil-Jaurena
Maribel Clemente
Simon Urschel
Lori West
Marjorie Pion
Rafael Correa-Rocha
author_sort Jacobo López-Abente
title Basiliximab impairs regulatory T cell (TREG) function and could affect the short-term graft acceptance in children with heart transplantation
title_short Basiliximab impairs regulatory T cell (TREG) function and could affect the short-term graft acceptance in children with heart transplantation
title_full Basiliximab impairs regulatory T cell (TREG) function and could affect the short-term graft acceptance in children with heart transplantation
title_fullStr Basiliximab impairs regulatory T cell (TREG) function and could affect the short-term graft acceptance in children with heart transplantation
title_full_unstemmed Basiliximab impairs regulatory T cell (TREG) function and could affect the short-term graft acceptance in children with heart transplantation
title_sort basiliximab impairs regulatory t cell (treg) function and could affect the short-term graft acceptance in children with heart transplantation
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/4c11fa0c07a241ce8f6dbe296a31b180
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