期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 42, 期 12, 页码 3322-3333出版社
WILEY
DOI: 10.1002/eji.201242770
关键词
Antigen-specific; cGVHD; Direct pathway; Indirect pathway; Regulatory T cells
类别
资金
- National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust
- King's College London
- British Heart Foundation
- Guy's & St. Thomas's Charity
- British Heart Foundation [RG/08/005/25303] Funding Source: researchfish
- Medical Research Council [MR/J006742/1, G0600698B] Funding Source: researchfish
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-2b specificity or specificity for BALB/c H-2d 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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