Immunomodulation by blockade of the TRANCE co-stimulatory pathway in murine allogeneic islet transplantation.

Details

Serval ID
serval:BIB_1118C8F3FF1A
Type
Article: article from journal or magazin.
Collection
Publications
Title
Immunomodulation by blockade of the TRANCE co-stimulatory pathway in murine allogeneic islet transplantation.
Journal
Transplant international
Author(s)
Wojtusciszyn A., Andres A., Morel P., Charvier S., Armanet M., Toso C., Choi Y., Bosco D., Berney T.
ISSN
1432-2277 (Electronic)
ISSN-L
0934-0874
Publication state
Published
Issued date
09/2009
Peer-reviewed
Oui
Volume
22
Number
9
Pages
931-939
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
We explore herein the effect of TNF-related activation-induced cytokine (TRANCE) co-stimulatory pathway blockade on islet survival after allograft transplantation. Expression of TRANCE on murine C57Bl/6 (B6) CD4+ T cells after allogeneic activation was analyzed by fluorescence-activated cell sorter (FACS). The effect of a TRANCE receptor fusion protein (TR-Fc) and anti-CD154 antibody (MR1) on B6 spleen cell proliferation after allogeneic activation was assessed by mixed lymphocyte reaction (MLR). Three groups of B6 mice were transplanted with allogeneic islets (DBA2): Control; short-term TR-Fc-treatment (days 0-4); and prolonged TR-Fc-treatment (days -1 to 13). Donor-specific transfusion (DST) was performed at the time of islet transplantation in one independent experiment. Transplantectomy samples were analyzed by immunohistochemistry. TRANCE expression was upregulated in stimulated CD4+ T cells in vitro. In MLR experiments, TR-Fc and MR1 both reduced spleen cell proliferation, but less than the combination of both molecules. Short-course TR-Fc treatment did not prolong islet graft survival when compared with controls (10.6 +/- 1.9 vs. 10.7 +/- 1.5 days) in contrast to prolonged treatment (20.7 +/- 3.2 days; P < 0.05). After DST, primary non function (PNF) was observed in half of control mice, but never in TR-Fc-treated mice. Immunofluorescence staining for Mac-1 showed a clear decrease in macrophage recruitment in the treated groups. TRANCE-targeting may be an effective strategy for the prolongation of allogeneic islet graft survival, thanks to its inhibitory effects on co-stimulatory signals and macrophage recruitment.
Keywords
Animals, CD4-Positive T-Lymphocytes/immunology, CD40 Ligand/biosynthesis, Cell Separation, Flow Cytometry, Graft Survival, Islets of Langerhans Transplantation/methods, Macrophages/metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Models, Biological, RANK Ligand/antagonists & inhibitors, RANK Ligand/metabolism, Spleen/cytology, Transplantation, Homologous
Pubmed
Web of science
Create date
14/06/2021 9:59
Last modification date
24/05/2024 12:56
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