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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Version: Final published version
Serval ID
serval:BIB_BEE1D86C8E62
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
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.
Journal
Frontiers in immunology
Author(s)
Govender L., Wyss J.C., Kumar R., Pascual M., Golshayan D.
ISSN-L
1664-3224
Publication state
Published
Issued date
2017
Peer-reviewed
Oui
Volume
8
Pages
421
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
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
Yes
Create date
16/05/2017 16:23
Last modification date
20/08/2019 15:33
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