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 - 1311
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.