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

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)3322–3333
JournalEuropean Journal of Immunology
Volume42
Issue number12
Early online date26 Oct 2012
DOIs
Publication statusPublished - Dec 2012

King's Authors

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.

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