Induction of allograft tolerance by monoclonal CD3 antibodies: a matter of timing.
Am J Transplant
; 12(11): 2909-19, 2012 Nov.
Article
en En
| MEDLINE
| ID: mdl-22882762
ABSTRACT
Despite remarkable progress in organ transplantation through the development of a wealth of immunosuppressive drugs highly effective at controlling acute rejection, two major problems still remain, the loss of transplants due to chronic rejection and the growing number of sensitized recipients due to previous transplants, transfusions or pregnancies. Induction of immune tolerance appears to be the only way to curb this complex situation. Here we describe that a therapy, already successfully used to restore immune tolerance to self-antigens in overt autoimmunity, is effective at promoting transplant tolerance. We demonstrate that a short low-dose course with CD3 antibodies started after transplantation, at the time of effector T cell priming to alloantigens, induces permanent acceptance of fully mismatched islet allografts. Mechanistic studies revealed that antigen-specific regulatory and effector T cells are differentially affected by the treatment. CD3 antibody treatment preferentially induces apoptosis of activated alloreactive T cells which is mandatory for tolerance induction. In contrast, regulatory T cells are relatively spared from CD3 antibody-induced depletion and can transfer antigen-specific tolerance thus arguing for their prominent role in sustaining long-term graft survival.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Islotes Pancreáticos
/
Complejo CD3
/
Tolerancia al Trasplante
/
Tolerancia Inmunológica
/
Anticuerpos Monoclonales
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Am J Transplant
Asunto de la revista:
TRANSPLANTE
Año:
2012
Tipo del documento:
Article
País de afiliación:
Francia