Engineered regulatory T cells prevent graft-versus-host disease while sparing the graft-versus-leukemia effect after bone marrow transplantation.
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.
Cao
Jiang
J
Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, No 99 West Huaihai Road, Xuzhou, Jiangsu Prov 221002, China.
Chen
Chong
C
Zeng
Lingyu
L
Li
Li
L
Li
Zhenyu
Z
Xu
Kailin
K
D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000502:physiology; D006086:Graft vs Host Disease / Q000517:prevention & control*; D020544:Graft vs Leukemia Effect; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D014161:Transduction, Genetic
D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors