Anti-CD154 mAb and rapamycin induce T regulatory cell mediated tolerance in xenogeneic islet transplantation : IXA-O-1.2

Details

Serval ID
serval:BIB_8BD2229C2EF8
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
Collection
Publications
Institution
Title
Anti-CD154 mAb and rapamycin induce T regulatory cell mediated tolerance in xenogeneic islet transplantation : IXA-O-1.2
Title of the conference
Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xenotransplantation-Association
Author(s)
Muller Yannick, Morel Philippe, Golshayan Déla, Seebach Jörg, Wekerle Thomas, Bühler Léo
Address
Venice, Italy, October 12-16, 2009
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
16
Series
Xenotransplantation
Pages
353
Language
english
Notes
Objective: Anti-CD154 (MR1) monoclonal antibody (mAb) and rapamycin
(RAPA) treatment were both shown to improve survival of concordant ratto-
mouse islet xenografts. The present study investigated rat-to-mouse islet
xenograft survival when MR1 and RAPA treatment were combined and
analyzed the role of CD4+CD25+Foxp3+ T regulatory cells (Treg) in the
induction and maintenance of the ensuing tolerance.
Research Design and Methods: RAPA MR1 treated mice received additional
IL-2, anti-IL2 mAb (n=14) or anti CD25 mAb either early (0-28 day) or
late (100-128 day) post-transplantation. Treg were characterised in the
blood, spleen, draining lymph nodes and within the graft of tolerant mice
and rejecting mice.
Results: Fourteen days of combination therapy with MR1 and RAPA
allowed indefinite islet graft survival. Additional administration of
IL-2, anti-IL-2 mAb or depleting anti-CD25 mAb at the time of
transplantation resulted in rejection, 100%, 100% and 89% respectively,
whereas administration at 100 ays post transplantation lead to lower
rejection rates (10%, 25% and 40% respectively). Tolerant mice showed
an increase of Treg within the graft and in draining lymph nodes early
post transplantation, whereas 100 days post transplantation no significant
increase of Treg was observed. Rejecting mice showed a transient
increase of Treg in the xenograft and secondary lymphoid organs
which disappeared within 7 days after rejection. Treg isolated from both
tolerant and rejecting recipients showed pronounced suppressive function
in vitro.
Conclusion: Treg might play a critical role in the induction of tolerance
early, but not in the maintenance of tolerance late after concordant islet
xenotransplantation.
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Create date
08/12/2009 15:25
Last modification date
13/01/2022 7:33
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