Alloantigen-specific regulatory T cells prevent experimental chronic graft-versus-host disease by simultaneous control of allo- and autoreactivity

Autor: Pervinder Sagoo, Yuen Tsang, Giovanna Lombardi, Robert I. Lechler, Linda Barber, Alistair Noble, Kulachelvy Ratnasothy
Rok vydání: 2012
Předmět:
Zdroj: European Journal of Immunology. 42:3322-3333
ISSN: 0014-2980
Popis: 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 haploidentical hematopoietic transplantation, as they allow persistence of donor T cells capable of responding to foreign antigens whilst preventing cGVHD-mediated autoimmunity.
Databáze: OpenAIRE
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