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
Institution
Title
Immunomodulation by blockade of the TRANCE co-stimulatory pathway in murine allogeneic islet transplantation
Journal
Transplant International
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
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 9:59
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18/09/2021 6:38