title: Suppression of graft-versus-host disease and retention of graft-versus-tumour reaction by murine genetically engineered dendritic cells following bone marrow transplantation.
abstract: The effect of infusion of lentiviral vector‑mediated, genetically engineered dendritic cells (DCs) following allogeneic bone marrow transplantation (allo‑BMT) on graft‑versus‑host disease (GVHD) and graft‑versus‑leukemia (GVL) was investigated in a mouse model. Lentivirus‑mediated expression of soluble tumor necrosis factor receptor 1 (sTNFR1) converted immature DCs (imDCs) from BABL/c mice into engineered DCs in vitro. An EL4 leukemia allo‑BMT model of BABL/c to C57BL/6 mice was established. Engineered DCs with donor bone marrow cells and splenocytes were subsequently transplanted into myeloablatively irradiated recipients. The average survival duration in the sTNFR1‑ and pXZ9‑imDC groups was significantly prolonged compared with that of the allo‑BMT group (P<0.05). Mild histological changes in GVHD or leukemia were observed in the recipients in the sTNFR1‑imDC group and clinical GVHD scores in this group were significantly decreased compared with those of the transplantation and pXZ9‑imDC groups. Serum interferon‑γ levels were decreased in the pXZ9‑imDC and sTNFR1‑imDC groups compared with those in the allo‑BMT group (P<0.05), with the reduction being more significant in the sTNFR1‑imDC group (P<0.05). Serum interleukin‑4 expression levels were decreased in the allo‑BMT group, but gradually increased in the pXZ9‑imDC and sTNFR1‑imDC groups (P<0.05). Co‑injection of donor genetically‑engineered imDCs was able to efficiently protect recipient mice from lethal GVHD while preserving GVL effects during allo‑BMT.
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Yihong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Hematology, Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, P.R. China.
authors.forename: Saran
authors.initials: S
authors.lastname: Feng
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Wanru
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Depeng
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Qunxian
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Xu
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002470:Cell Survival; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D006086:Graft vs Host Disease / Q000209:etiology* / Q000378:metabolism / Q000628:therapy; D007165:Immunosuppression Therapy / Q000379:methods; D016086:Lentivirus / Q000235:genetics; D007938:Leukemia / Q000150:complications / Q000628:therapy; D008297:Male; D051379:Mice; D014161:Transduction, Genetic; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines