INVESTIGADORES
PERONE Marcelo Javier
artículos
Título:
Use of the inhibitory effect of apoptotic cells on dendritic cells for graft survival via T cell deletion and regulatory T cells
Autor/es:
WANGA, Z.; LARREGINA, A. T.; SHUFESKYA, W. J.; PERONE, M. J.; MONTECALVO, A.; ZAHORCHAK, A. F.; THOMSON, A. W.; MORELLI, A. E.
Revista:
AMERICAN JOURNAL OF TRANSPLANTATION
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Lugar: Wiley-Blackwell Publishing, Inc; Año: 2006 p. 1297 - 1297
ISSN:
1600-6135
Resumen:
Abstract Tolerance induction against donor allo-antigens (allo- Ag) remains one of the most challenging aspects of transplant immunology. The ability of dendritic cells (DC) to participate in immunity and tolerance makes them an excellent tool for tolerance induction. Here, we employed the immunosuppressive properties of apoptotic cells to deliver simultaneously an inhibitory signal and donor allo-Ag to recipient DC for treatment of allograft rejection. DC that captured apoptotic cells remained immature and activated deficiently anti-donor CD4+ T cells that were unable to upregulate T-cell activation markers, to secrete IL-2 and IFNc+ T cells that were unable to upregulate T-cell activation markers, to secrete IL-2 and IFNcc and to survive under homeostatic conditions due to low expression of Bcl-XL, IL-7R and IL-15R. Administration of donor apoptotic cells decreased the systemic anti-donor T- and B-cell response and prolonged cardiac allograft survival in mice. The effect was donor specific and required the interaction of donor apoptotic cells with recipient quiescent CD8a + DC. When combined with CD40-CD154-blockade, administration of donor apoptotic cells resulted in indefinite graft survival mediated by generation of regulatory T cells. The use of the inhibitory effects of apoptotic cells on the anti-donor response provides a new approach to treat transplant rejection.L, IL-7R and IL-15R. Administration of donor apoptotic cells decreased the systemic anti-donor T- and B-cell response and prolonged cardiac allograft survival in mice. The effect was donor specific and required the interaction of donor apoptotic cells with recipient quiescent CD8a + DC. When combined with CD40-CD154-blockade, administration of donor apoptotic cells resulted in indefinite graft survival mediated by generation of regulatory T cells. The use of the inhibitory effects of apoptotic cells on the anti-donor response provides a new approach to treat transplant rejection.a + DC. When combined with CD40-CD154-blockade, administration of donor apoptotic cells resulted in indefinite graft survival mediated by generation of regulatory T cells. The use of the inhibitory effects of apoptotic cells on the anti-donor response provides a new approach to treat transplant rejection.
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