IL-2-Mediated In Vivo Expansion of Regulatory T Cells Combined with CD154-CD40 Co-Stimulation Blockade but Not CTLA-4 Ig Prolongs Allograft Survival in Naive and Sensitized Mice.

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_BEE1D86C8E62
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
IL-2-Mediated In Vivo Expansion of Regulatory T Cells Combined with CD154-CD40 Co-Stimulation Blockade but Not CTLA-4 Ig Prolongs Allograft Survival in Naive and Sensitized Mice.
Périodique
Frontiers in immunology
Auteur(s)
Govender L., Wyss J.C., Kumar R., Pascual M., Golshayan D.
ISSN-L
1664-3224
Statut éditorial
Publié
Date de publication
2017
Peer-reviewed
Oui
Volume
8
Pages
421
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
In recent years, regulatory T cells (Treg)-based immunotherapy has emerged as a promising strategy to promote operational tolerance after solid organ transplantation (SOT). However, a main hurdle for the therapeutic use of Treg in transplantation is their low frequency, particularly in non-lymphopenic hosts. We aimed to expand Treg directly in vivo and determine their efficacy in promoting donor-specific tolerance, using a stringent experimental model. Administration of the IL-2/JES6-1 immune complex at the time of transplantation resulted in significant expansion of donor-specific Treg, which suppressed alloreactive T cells. IL-2-mediated Treg expansion in combination with short-term CD154-CD40 co-stimulation blockade, but not CTLA-4 Ig or rapamycin, led to tolerance to MHC-mismatched skin grafts in non-lymphopenic mice, mainly by hindering alloreactive CD8(+) effector T cells and the production of alloantibodies. Importantly, this treatment also allowed prolonged survival of allografts in the presence of either donor-specific or cross-reactive memory cells. However, late rejection occurred in sensitized hosts, partly mediated by activated B cells. Overall, these data illustrate the potential but also some important limitations of Treg-based therapy in clinical SOT as well as the importance of concomitant immunomodulatory strategies in particular in sensitized hosts.

Pubmed
Web of science
Open Access
Oui
Création de la notice
16/05/2017 16:23
Dernière modification de la notice
20/08/2019 15:33
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