Involvement of graft-derived interleukin-15 in islet allograft rejection in mice.
Cytokine
; 34(1-2): 106-13, 2006 Apr.
Article
em En
| MEDLINE
| ID: mdl-16723256
ABSTRACT
The possibility that islets play a role in graft rejection during islet transplantation for type-1 diabetes patients holds promise for ex vivo islet manipulation and for specific anti-rejection therapy. Interleukin (IL)-15 is a T cell growth factor and chemoattractant that is expressed by non-T cells. Intragraft expression of IL-15 is elevated during acute rejection in patients and in mice, and systemic blockade of IL-15 in mice prolongs allograft survival. However, the source of IL-15 in these conditions is undetermined. Since epithelial cell-derived IL-15 promotes lymphocyte proliferation in culture, we sought to determine whether islet-derived IL-15 promotes rejection in mice. We designed antisense oligodeoxyribonucleotide molecules that target mouse IL-15. Uptake of FITC-labeled antisense molecules and efficacy of IL-15 inhibition in IFNgamma-stimulated islets were evaluated. Islets exhibited typical cytoplasmatic distribution of antisense molecules and produced IL-15 levels that were comparable to non-stimulated cells. Antisense-treated islet allografts, that were transplanted across multiple minor-histocompatibility-antigen mismatched strains of mice, were accepted at a higher rate than control-antisense treated islets or untreated islets (88.9% vs. 37.5% and 20%, respectively). Our results suggest that islet-derived IL-15 may be involved in acute islet allograft rejection.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transplante das Ilhotas Pancreáticas
/
Ilhotas Pancreáticas
/
Interleucina-15
Limite:
Animals
Idioma:
En
Revista:
Cytokine
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Israel