Regulatory T cells (Tregs) can prevent graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). Here we developed a lentivirus-based strategy to ectopically express Foxp3 in mouse CD4(+)CD25(-) T cells. These cells shared similar immunophenotypes and biological features of natural Tregs. Co-injection of engineered Tregs with donor bone marrow cells and splenocytes prevented recipients from lethal GVHD. Furthermore, we showed that graft-versus-leukemia (GVL) effect against EL4/DsRed leukemic cells was maximally preserved while GVHD was minimized during exposure to engineered Tregs in a mouse leukemia model. These findings provide a novel approach to preventing GVHD while maintaining GVL effect during BMT.
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