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Unraveling the Crucial Roles of FoxP3+ Regulatory T Cells in Vascularized Composite Allograft Tolerance Induction and Maintenance.

Authors :
Anggelia MR
Cheng HY
Chuang WY
Hsieh YH
Wang AYL
Lin CH
Wei FC
Brandacher G
Lin CH
Source :
Transplantation [Transplantation] 2021 Jun 01; Vol. 105 (6), pp. 1238-1249.
Publication Year :
2021

Abstract

Background: The role of regulatory T cells (Treg) in tolerance induction of vascularized composite allotransplantation (VCA) remains unclear. This study was designed to examine characteristics of Treg after VCA and their capacity to rescue allografts from rejection.<br />Methods: Osteomyocutaneous allografts were transplanted from Balb/c to C57BL/6 mice. All mice received costimulatory blockade and a short course of rapamycin. To elucidate the role of Treg for tolerance induction, Treg depletion was performed at postoperative day (POD) 0, 30, or 90. To assess capacity of Treg to rescue allografts from rejection, an injection of 2 × 106 Treg isolated from tolerant mice was applied.<br />Results: Eighty percent of VCA recipient mice using costimulatory blockade and rapamycin regimen developed tolerance. The tolerant recipients had a higher ratio of circulating Treg to effector T cells and elevated interleukin-10 at POD 30. A significantly higher rejection rate was observed when Treg were depleted at POD 30. But Treg depletion at POD 90 had no effect on tolerance. Treg from tolerant recipients showed stronger suppressive potential and the ability to rescue allografts from rejection. Furthermore, transplanted Treg-containing skin grafts from tolerant mice delayed rejection elicited by adoptively transferred effector T cells to Rag2-/- mice.<br />Conclusions: Circulating Treg are crucial for inducing VCA tolerance in the early posttransplant phase, and allograft-residing Treg may maintain tolerance. Treg may, therefore, serve as a potential cellular therapeutic to improve VCA outcomes.<br />Competing Interests: The authors declare no conflicts of interest.<br /> (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Details

Language :
English
ISSN :
1534-6080
Volume :
105
Issue :
6
Database :
MEDLINE
Journal :
Transplantation
Publication Type :
Academic Journal
Accession number :
33141809
Full Text :
https://doi.org/10.1097/TP.0000000000003509