In a murine model of systemic lupus erythematosus (SLE)-like chronic graft-versus-host disease (cGVHD), donor CD8 + T cells rapidly fall into anergy to host cells, while donor CD4 + T cells hyperactivate B cells and break B-cell tolerance to self-Ags in the recipient mouse. The functional recovery of donor CD8 + T cells can result in the conversion of cGVHD to acute GVHD (aGVHD), indicating that donor CD8 + T-cell anergy is a restriction factor in the development of cGVHD. In this report, we present evidence that donor CD4 + CD25 + regulatory T cells (T reg cells) are critical in maintaining the donor CD8 + T-cell anergy and thus suppressing the development of aGVHD in mice that are naturally prone to cGVHD. Our results provide a novel insight into the role of T reg cells in determining cGVHD versus aGVHD.
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