Literature DB >> 33436905

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

Jacobo López-Abente1, Marta Martínez-Bonet1, Esther Bernaldo-de-Quirós1, Manuela Camino2, Nuria Gil2, Esther Panadero2, Juan Miguel Gil-Jaurena3, Maribel Clemente4, Simon Urschel5,6,7, Lori West5,6,7, Marjorie Pion1, Rafael Correa-Rocha8,9.   

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.

Entities:  

Year:  2021        PMID: 33436905      PMCID: PMC7803770          DOI: 10.1038/s41598-020-80567-9

Source DB:  PubMed          Journal:  Sci Rep        ISSN: 2045-2322            Impact factor:   4.379


  48 in total

1.  Regulatory T cells in kidney transplant recipients: the effect of induction immunosuppression therapy.

Authors:  Eva Krystufkova; Alena Sekerkova; Ilja Striz; Irena Brabcova; Eva Girmanova; Ondrej Viklicky
Journal:  Nephrol Dial Transplant       Date:  2011-12-13       Impact factor: 5.992

2.  Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression.

Authors:  Yisong Y Wan; Richard A Flavell
Journal:  Nature       Date:  2007-01-14       Impact factor: 49.962

3.  Risk stratification to determine the impact of induction therapy on survival, rejection and adverse events after pediatric heart transplant: A multi-institutional study.

Authors:  Chesney Castleberry; Elizabeth Pruitt; Rebecca Ameduri; Kenneth Schowengerdt; Erik Edens; Nancy Hagin; James K Kirklin; David Naftel; Simon Urschel
Journal:  J Heart Lung Transplant       Date:  2017-05-11       Impact factor: 10.247

4.  Regulatory T cells induced by 1 alpha,25-dihydroxyvitamin D3 and mycophenolate mofetil treatment mediate transplantation tolerance.

Authors:  S Gregori; M Casorati; S Amuchastegui; S Smiroldo; A M Davalli; L Adorini
Journal:  J Immunol       Date:  2001-08-15       Impact factor: 5.422

5.  Reduction of the occurrence of acute cellular rejection among renal allograft recipients treated with basiliximab, a chimeric anti-interleukin-2-receptor monoclonal antibody. United States Simulect Renal Study Group.

Authors:  B D Kahan; P R Rajagopalan; M Hall
Journal:  Transplantation       Date:  1999-01-27       Impact factor: 4.939

6.  Pharmacokinetics and pharmacodynamics of basiliximab in Japanese pediatric renal transplant patients.

Authors:  T Nagai; Y Gotoh; Y Watarai; T Tajima; K Arai; K Uchida
Journal:  Int J Clin Pharmacol Ther       Date:  2010-03       Impact factor: 1.366

7.  A function for interleukin 2 in Foxp3-expressing regulatory T cells.

Authors:  Jason D Fontenot; Jeffrey P Rasmussen; Marc A Gavin; Alexander Y Rudensky
Journal:  Nat Immunol       Date:  2005-10-16       Impact factor: 25.606

8.  Disposition of basiliximab, an interleukin-2 receptor monoclonal antibody, in recipients of mismatched cadaver renal allografts.

Authors:  J Kovarik; P Wolf; J M Cisterne; G Mourad; Y Lebranchu; P Lang; B Bourbigot; D Cantarovich; D Girault; C Gerbeau; A G Schmidt; J P Soulillou
Journal:  Transplantation       Date:  1997-12-27       Impact factor: 4.939

9.  Adoptive transfer of double negative T regulatory cells induces B-cell death in vivo and alters rejection pattern of rat-to-mouse heart transplantation.

Authors:  Yuexia Ma; Kathy M He; Bertha Garcia; Weiping Min; Anthony Jevnikar; Zhu-Xu Zhang
Journal:  Xenotransplantation       Date:  2008-02       Impact factor: 3.907

10.  Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting.

Authors:  H Schorle; T Holtschke; T Hünig; A Schimpl; I Horak
Journal:  Nature       Date:  1991-08-15       Impact factor: 49.962

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  4 in total

1.  A Novel GMP Protocol to Produce High-Quality Treg Cells From the Pediatric Thymic Tissue to Be Employed as Cellular Therapy.

Authors:  Esther Bernaldo-de-Quirós; Beatriz Cózar; Rocío López-Esteban; Maribel Clemente; Juan Miguel Gil-Jaurena; Carlos Pardo; Ana Pita; Ramón Pérez-Caballero; Manuela Camino; Nuria Gil; María Eugenia Fernández-Santos; Susana Suarez; Marjorie Pion; Marta Martínez-Bonet; Rafael Correa-Rocha
Journal:  Front Immunol       Date:  2022-05-16       Impact factor: 8.786

Review 2.  A New Generation of Cell Therapies Employing Regulatory T Cells (Treg) to Induce Immune Tolerance in Pediatric Transplantation.

Authors:  Esther Bernaldo-de-Quirós; Marjorie Pion; Marta Martínez-Bonet; Rafael Correa-Rocha
Journal:  Front Pediatr       Date:  2022-05-11       Impact factor: 3.569

3.  The Presence of a Marked Imbalance Between Regulatory T Cells and Effector T Cells Reveals That Tolerance Mechanisms Could Be Compromised in Heart Transplant Children.

Authors:  Esther Bernaldo-de-Quirós; Jacobo López-Abente; Manuela Camino; Nuria Gil; Esther Panadero; Rocío López-Esteban; Marta Martínez-Bonet; Marjorie Pion; Rafael Correa-Rocha
Journal:  Transplant Direct       Date:  2021-04-23

4.  Immune Reconstitution of Patients Who Recovered From Steroid-Refractory Acute Graft-Versus-Host Disease After Basiliximab Treatment.

Authors:  Dao-Xing Deng; Shuang Fan; Xiao-Hui Zhang; Lan-Ping Xu; Yu Wang; Chen-Hua Yan; Huan Chen; Yu-Hong Chen; Wei Han; Feng-Rong Wang; Jing-Zhi Wang; Xu-Ying Pei; Ying-Jun Chang; Kai-Yan Liu; Xiao-Jun Huang; Xiao-Dong Mo
Journal:  Front Oncol       Date:  2022-07-15       Impact factor: 5.738

  4 in total

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