title: Suppression of lentivirus-mediated transgenic dendritic cells in graft-versus-host disease after allogeneic bone marrow transplantation in mice.
abstract: We determined whether genetically engineered immature dendritic cells (imDCs) mediated by lentiviral vectors alleviate acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (allo-BMT) in mice. We introduced the mouse chemokine receptor 7 (Ccr7) gene into the bone marrow-derived imDCs of C57BL/6 mice to construct genetically engineered imDCs. A 1:1 mixture of bone marrow and spleen cells from the donors was injected into the recipients, which were divided into four groups: radiation, transplantation, empty vector, and transgenic imDC groups. Symptoms, clinical scores, GVHD pathological changes, and survival times and rates of recipients were recorded; secretion of IFN-γ and IL-4, and allogeneic chimerism rates were detected. The survival time of the transgenic imDC group (27.5 ± 7.55 days) was significantly longer than in the other three groups (P < 0.01). The GVHD score of the imDC group mice was significantly lower than in the transplantation and empty vector groups (P < 0.05), which meant that mice in the transgenic imDC group had the lightest pathology damage in the target organs. In the transplantation group, IFN-γ increased while IL-4 decreased. In contrast, IFN-γ decreased and IL-4 increased in both empty vector and trans-imDC groups, and the difference was significant in the latter (P < 0.01). Thirty days or more following transplantation, the allogeneic chimerism rate was still 95-100%, suggesting complete donor type implantation. Ccr7 transfection into imDCs suppressed occurrence and severity of acute GVHD after allo-BMT in mice; the mechanism might be associated with IFN-γ decrease and IL-4 increase.
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Xu
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: W R
authors.initials: WR
authors.lastname: Chen
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: D P
authors.initials: DP
authors.lastname: Li
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: L X
authors.initials: LX
authors.lastname: Song
authors.affiliation: Department of Hematology, The Third Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: J Q
authors.initials: JQ
authors.lastname: Wu
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: P
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Li
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Y H
authors.initials: YH
authors.lastname: Huang
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002465:Cell Movement; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology*; D006086:Graft vs Host Disease / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D016086:Lentivirus; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009928:Organ Specificity; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000166:cytology; D014184:Transplantation, Homologous
chemical_list: D015847:Interleukin-4; D007371:Interferon-gamma