Alloantigen-specific regulatory T cells prevent experimental chronic graft-versus-host disease by simultaneous control of allo- and autoreactivity.
Eur J Immunol
; 42(12): 3322-33, 2012 Dec.
Article
en En
| MEDLINE
| ID: mdl-22996319
ABSTRACT
Chronic graft-versus-host disease (cGVHD) is characterised by a complex etiology of both alloimmune- and autoimmune-mediated disease progression and pathology, and is consequently difficult to control. The therapeutic potential of regulatory T (Treg) cells for cGVHD is currently being investigated; however, the relative ability of Treg cells with defined antigen specificities for auto- and alloantigen to prevent disease has not been previously examined. In this study, we show that donor-derived Treg-cell lines generated with self-MHC H-2(b) specificity or specificity for BALB/c H-2(d) alloantigen presented via the direct or indirect pathways are able to mediate an equal protection against cGVHD immune pathology in a disease model associated with recipient B-cell-driven humoral autoimmunity and glomerulonephritis. Mechanistically, autospecific Treg cells prevented disease induction by blocking donor T-cell engraftment whereas allospecific Treg cells permitted long-term engraftment of donor T cells. Donor T cells, while unresponsive to auto- and recipient alloantigens, retained the capacity to respond to third party alloantigens on ex vivo stimulation. These findings indicate that allospecific Treg cells may therefore be more clinically relevant as a cell therapy for cGVHD in the context of haplo-identical hematopoietic transplantation, as they allow persistence of donor T cells capable of responding to foreign antigens whilst preventing cGVHD-mediated autoimmunity.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Antígenos H-2
/
Autoinmunidad
/
Linfocitos T Reguladores
/
Enfermedad Injerto contra Huésped
/
Isoantígenos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Reino Unido