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.
Journal
Transplantation direct
ISSN: 2373-8731
Titre abrégé: Transplant Direct
Pays: United States
ID NLM: 101651609
Informations de publication
Date de publication:
May 2021
May 2021
Historique:
received:
08
02
2021
revised:
05
03
2021
accepted:
06
03
2021
entrez:
30
4
2021
pubmed:
1
5
2021
medline:
1
5
2021
Statut:
epublish
Résumé
Regulatory T cells (Treg) are crucial for the induction and maintenance of graft tolerance. In pediatric heart transplant procedures, the thymus is routinely excised, removing the primary source of T-cell replenishment. Consequently, thymectomy joined to the effects of immunosuppression on the T-cell compartment may have a detrimental impact on Treg values, compromising the intrinsic tolerance mechanisms and the protective role of Treg preventing graft rejection in heart transplant children. A prospective study including 7 heart transplant children was performed, and immune cell populations were evaluated periodically in fresh peripheral blood at different time points before and up to 3 y posttransplant. Treg counts decreased significantly from the seventh-month posttransplant. Furthermore, there was a significant increase in effector memory and terminally differentiated effector memory T cells coinciding with the fall of Treg counts. The Treg/Teffector ratio, a valuable marker of the tolerance/rejection balance, reached values around 90% lower than pretransplant values. Additionally, a negative correlation between Treg count and T effector frequency was observed. Particularly, when Treg count decreases below 50 or 75 cells/μL in the patients, the increase in the frequency of T effector CD4+ and CD8+, respectively, experiences a tipping point, and the proportion of T-effector cells increases dramatically. These results reveal that interventions employed in pediatric heart transplantation (immunosuppression and thymectomy) could induce, as an inevitable consequence, a dysregulation in the immunologic status characterized by a marked imbalance between Treg and T effector, which could jeopardize the preservation of tolerance during the period with the higher incidence of acute rejection.
Identifiants
pubmed: 33928185
doi: 10.1097/TXD.0000000000001152
pmc: PMC8078462
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e693Informations de copyright
Copyright © 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.
Déclaration de conflit d'intérêts
This work was supported by grants from “Fundación Familia Alonso” (FFA-FIBHGM 2019), Instituto de Salud Carlos III (ISCIII) cofinanced by FEDER funds (ICI20/00063; PI18/00495; DTS18/00038, PI18/00506). E.B.-Q. was supported by a grant from Comunidad de Madrid (EXOHEP-CM. B2017/BMD3727). J.L.-A. was supported by an IISGM predoctoral grant. M.M.-B. was supported by the Sara Borrell Program from ISCIII (CD18/00105). The other authors declare no conflicts of interest.
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