Effects of immature dendritic cells to express CCR7 on graft-versus-host disease in allogeneic bone marrow transplant mouse model
Author(s): LI Depeng, WU Jiaqing, HUANG Yihong, SONG Lixiao, GU Honghong, GAO Cailing, LI Zhenyu, PAN Xiuying, XU Kailin
Pages: 782-787
Year: 2013 Issue: 9
Journal: Chinese Journal of Hematology
Keyword: Dendritic cells; Gene; CCR7; Bone marrow transplant; Mice; Graft vs host disease;
Abstract: Objective To investigate the effects of immature dendritic cells (imDC) expressing chemokine receptor-7 (CCR7) on acute graft-versus-host disease (aGVHD)in allogeneic bone marrow transped (allo-BMT) mouse model.Methods We constructed the lentiviral vectors carrying mouse CCR7 gene and infect imDC effectively in vitro.GVHD model was established with C57BL/6(H-2b) donor mice and BALB/c (H-2d) recipient mice.After irradiation,recipients were injected with donor bone marrow and spleen cells along with CCR7-modified dendritic cells.Mice were randomized into irradiation,transplant control,pXZ9-imDC (empty vector control) and CCR7-imDC groups.Survival,GVHD score,histopathological analysis and plasma levels of inflammatory cytokines were observed.Results The mean survival in irradiation,transplantation,pXZ9-imDC and CCR7-imDC groups were (8.20± 1.48)d,(12.20± 2.78) d,(20.70 ± 6.01)d and (27.5 ± 7.55)d respectively.The survival in CCR7-imDC group was significantly improved compared with other groups (P＜0.05).GVHD scores in transplantation,pXZ9-imDC and CCR7-imDC groups were (6.90± 1.66),(5.60±0.97) and (4.10± 1.79) respectively.CCR7-imDC group had significantly lower GVHD score and minor tissue damages shown by histopathological analysis than the other groups.Plasma IFN-γ level increased and reached the peak at +10 day in transplant group,while it gradually decreased in pXZ9-imDC and CCR7-imDC groups,and then reached the nadir at +20 day post-allo-BMT,with the lowest level in CCR7-imDC group (P＜0.01).Plasma IL-4 decreased in transplant group,while it gradually increased in pXZ9-imDC and CCR7-imDC groups and reached the highest level at + 10 day in CCR7-imDC group (P＜0.01).The 95％-100％ of H-2b positive cells in recipient mice on + 30 day post-allo-BMT demonstrated the complete donor-type implantation.Conclusion Genetically modified immature DC by CCR7 gene could alleviate damages by GVHD and prolong survival of recipient mice after allo-BMT.
Pages: 782-787
Year: 2013 Issue: 9
Journal: Chinese Journal of Hematology
Keyword: Dendritic cells; Gene; CCR7; Bone marrow transplant; Mice; Graft vs host disease;
Abstract: Objective To investigate the effects of immature dendritic cells (imDC) expressing chemokine receptor-7 (CCR7) on acute graft-versus-host disease (aGVHD)in allogeneic bone marrow transped (allo-BMT) mouse model.Methods We constructed the lentiviral vectors carrying mouse CCR7 gene and infect imDC effectively in vitro.GVHD model was established with C57BL/6(H-2b) donor mice and BALB/c (H-2d) recipient mice.After irradiation,recipients were injected with donor bone marrow and spleen cells along with CCR7-modified dendritic cells.Mice were randomized into irradiation,transplant control,pXZ9-imDC (empty vector control) and CCR7-imDC groups.Survival,GVHD score,histopathological analysis and plasma levels of inflammatory cytokines were observed.Results The mean survival in irradiation,transplantation,pXZ9-imDC and CCR7-imDC groups were (8.20± 1.48)d,(12.20± 2.78) d,(20.70 ± 6.01)d and (27.5 ± 7.55)d respectively.The survival in CCR7-imDC group was significantly improved compared with other groups (P＜0.05).GVHD scores in transplantation,pXZ9-imDC and CCR7-imDC groups were (6.90± 1.66),(5.60±0.97) and (4.10± 1.79) respectively.CCR7-imDC group had significantly lower GVHD score and minor tissue damages shown by histopathological analysis than the other groups.Plasma IFN-γ level increased and reached the peak at +10 day in transplant group,while it gradually decreased in pXZ9-imDC and CCR7-imDC groups,and then reached the nadir at +20 day post-allo-BMT,with the lowest level in CCR7-imDC group (P＜0.01).Plasma IL-4 decreased in transplant group,while it gradually increased in pXZ9-imDC and CCR7-imDC groups and reached the highest level at + 10 day in CCR7-imDC group (P＜0.01).The 95％-100％ of H-2b positive cells in recipient mice on + 30 day post-allo-BMT demonstrated the complete donor-type implantation.Conclusion Genetically modified immature DC by CCR7 gene could alleviate damages by GVHD and prolong survival of recipient mice after allo-BMT.
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