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

Details

Serval ID
serval:BIB_0E1D7A0A344D
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
0934-0874
Publication state
Published
Issued date
09/2009
Volume
22
Number
9
Pages
931-939
Language
english
Notes
479lm
Times Cited:8
Cited References Count:28
Abstract
P>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
co-stimulatory blockade, islet transplantation, tnf-related activation-induced cytokine, activation-induced cytokine, long-term survival, tnf family-member, tumor-necrosis-factor, humanized anti-cd154, allograft-rejection, monoclonal-antibody, nonhuman-primates, graft-survival, dendritic cell
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14/06/2021 8:59
Last modification date
18/09/2021 5:38
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