Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/11255
Title: Prolonged xenograft survival induced by inducible costimulator-Ig is associated with increased forkhead box P3(+) cells.
Austin Authors: Hodgson, Russell;Christiansen, Dale;Ziolkowski, Andrew;Mouhtouris, Effie ;Simeonovic, Charmaine J;Ierino, Francesco L;Sandrin, Mauro S 
Affiliation: Northern Health, Victoria, Australia
Surgery (University of Melbourne)
Issue Date: 27-May-2011
Publication information: Transplantation; 91(10): 1090-7
Abstract: Blockade of the inducible costimulator (ICOS) pathway has been shown to prolong allograft survival; however, its utility in xenotransplantation is unknown. We hypothesize that local expression of ICOS-Ig by the xenograft will suppress the T-cell response resulting in significant prolonged graft survival.Pig iliac artery endothelial cells (PIEC) secreting ICOS-Ig were generated and examined for the following: (1) inhibition of allogeneic and xenogeneic proliferation of primed T cells in vitro and (2) prolongation of xenograft survival in vivo. Grafts were examined for Tregs by flow cytometry and cytokine levels determined by quantitative reverse-transcriptase polymerase chain reaction.Soluble ICOS-Ig markedly decreased allogeneic and xenogeneic primed T-cell proliferation in a dose-dependent manner. PIEC-ICOS-Ig grafts were significantly prolonged compared with wild-type grafts (median survival, 34 and 12 days, respectively) with 20% of PIEC-ICOS-Ig grafts surviving more than 170 days. Histological examination showed a perigraft cellular accumulation of Forkhead box P3 (Foxp3(+)) cells in the PIEC-ICOS-Ig grafts, these were also shown to be CD3(+)CD4(+)CD25(+). Survival of wild-type PIEC grafts in a recipient simultaneously transplanted with PIEC-ICOS-Ig were also prolonged, with a similar accumulation of Foxp3(+) cells at the periphery of the graft demonstrating ICOS-Ig induces systemic graft prolongation. However, this prolongation was specific for the priming xenograft. Intragraft cytokine analysis showed an increase in interleukin-10 levels, suggesting a potential role in induction/function of CD4(+)CD25(+)Foxp3(+) cells.This study demonstrates prolonged xenograft survival by local expression of ICOS-Ig, we propose that the accumulation of CD4(+)CD25(+)Foxp3(+) cells at the periphery of the graft and secretion of interleukin-10 is responsible for this novel observation.
URI: https://ahro.austin.org.au/austinjspui/handle/1/11255
DOI: 10.1097/TP.0b013e31821774e0
ORCID: 
Journal: Transplantation
URL: https://pubmed.ncbi.nlm.nih.gov/21544030
Type: Journal Article
Subjects: Animals
Antigens, Differentiation, T-Lymphocyte.genetics.immunology
Cells, Cultured
Cytokines.genetics.metabolism
Endothelial Cells.immunology.transplantation
Female
Flow Cytometry
Forkhead Transcription Factors.metabolism
Gene Expression Regulation
Graft Rejection.immunology.prevention & control
Graft Survival
Humans
Immunoglobulin G.biosynthesis.immunology
Inducible T-Cell Co-Stimulator Protein
Interleukin-2 Receptor alpha Subunit.metabolism
Lymphocyte Culture Test, Mixed
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes, Regulatory.immunology
Time Factors
Transfection
Transplantation, Heterologous
Appears in Collections:Journal articles

Show full item record

Page view(s)

24
checked on May 21, 2024

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.