Costimulation blockade-induced cardiac allograft tolerance: inhibition of T cell expansion and accumulation of intragraft cD4(+)Foxp3(+) T cells.
Transplantation
; 82(11): 1493-500, 2006 Dec 15.
Article
en En
| MEDLINE
| ID: mdl-17164722
ABSTRACT
BACKGROUND:
Previous studies have demonstrated that anti-CD40L or anti-B7 requires the presence of CD4(+)CD25(+) regulatory T cells (Treg) to induce antigen specific hyporesponsiveness. Other tolerance strategies involving Treg have shown a dependency on interleukin (IL)-10. The objective of this study was to investigate the role of CD4(+)CD25(+) Treg and IL-10 when treating transplant recipients with cytotoxic T lymphocyte-associated antigen (CTLA)-4 immunoglobulin (Ig), anti-CD40L, and anti-lymphocyte function-associated antigen (LFA)-1.METHODS:
Recombinase activating gene-deficient (Rag1(-/-) mice were transplanted with BALB/c hearts and adoptively transferred with IL-10(-/-) CD4(+) T cells, CD4(+)CD25(-) T cells or CD4(+)CD25(-)CD103(-) T cells and treated with costimulation blockade. Intragraft T cells from C57BL/6 recipients were analyzed for the expression of the Foxp3 protein after tolerance induction.RESULTS:
Mice reconstituted with IL-10(-/-) CD4(+) T cells, CD4(+)CD25(-) T cells or CD4(+)CD25(-) CD103(-) T cells and treated with costimulation blockade accepted allografts permanently. Analysis of cells from recipient mice adoptively transferred with CD4(+)CD25(-) T cells contained a population of CD4(low)CD25(+) T cells 100 days after transplantation. Costimulation blockade partially prevented the homeostatic proliferation of CD4(+)CD25(-)CD103(-) T cells in Rag-1(-/-) recipients. Accepted allografts contained an elevated number of CD4(+)Foxp3(+) T cells.CONCLUSIONS:
These results indicate that T-cell derived IL-10 is not essential for induction of graft acceptance in mice treated with costimulation blockade, but that treatment limits T-cell expansion in the recipients. The results further indicate that tolerance is maintained by intragraft CD4(+)Foxp3(+) T cells.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inmunoglobulina G
/
Antígenos de Diferenciación
/
Antígenos CD
/
Trasplante de Corazón
/
Linfocitos T Reguladores
/
Tolerancia al Trasplante
/
Supervivencia de Injerto
Límite:
Animals
Idioma:
En
Revista:
Transplantation
Año:
2006
Tipo del documento:
Article
País de afiliación:
Suecia