title: [Influence of mouse genetic engineering regulatory T cells infusion on post-allogeneic bone marrow transplantation acute graft-versus-host disease in mice].
abstract: OBJECTIVE
  To explore the influence of the lentiviral vector mediated mouse genetic engineering regulatory T cells (Treg) infusion on post-allogeneic bone marrow transplantation (allo-BMT) acute graft-versus-host disease (GVHD) in mice.
  
  
  METHODS
  Lentivirus-mediated Forkhead box P3 (Foxp3) gene was transduced into BALB/c mice CD4(+)CD25(-) T cells (Treg) to construct engineered Tregs in vitro. An allo-BMT model of BALB/c to C57BL/6 mice was established. After irradiation, the recipients were injected with donor cells plus the genetic engineering Tregs. Survival time, clinical GVHD score, histopathological findings, activation of donor T cells or serum levels of inflammatory cytokines were observed after allo-BMT.
  
  
  RESULTS
  The mean survival times for radiation alone group (Gp I), transplantation control group (Gp II), engineering Treg infusion group (Gp III) and empty vector control group (Gp IV) were (8.8 ± 0.6) d, (36.7 ± 2.5) d, (51.6 ± 4.0) d and (34.1 ± 2.3) d, respectively. The survival time was significantly longer in Gp III than in other groups (P < 0.05). Histopathological finding in several target organs (skin, liver and small intestine) confirmed the presence of severe GVHD in Gp II and Gp IV, while no histological signs of GVHD were observed in long survival recipients in Gp III, and clinical GVHD scores in Gp III were significantly lower than that in Gps II and IV. The numbers of donor T cells and the percentage of IFN-producing donor T cells in the spleen of recipients in Gp III were significant lower than those in Gps II and IV at days 3 and 4, and at day 3 after transplantation, respectively (P < 0.05). The serum levels of IFN-γ, IL-2 and TNF-α were increased at day 21 to 28 after transplantation in all groups. The peak concentrations of IFN-γ, IL-2 and TNF-α in Gp III were significantly lower than those in Gps II and IV control groups at day 21 (P < 0.05).
  
  
  CONCLUSIONS
  Co-injection of genetic engineering Treg can efficiently prevent recipients from lethal GVHD after allo-BMT in mice by inhibiting the early activation and expansion of donor T cells and reducing the serum levels of inflammatory cytokines.
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Cao
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Chong
authors.initials: C
authors.lastname: Chen
authors.forename: Ling-yu
authors.initials: LY
authors.lastname: Zeng
authors.forename: Zhen-yu
authors.initials: ZY
authors.lastname: Li
authors.forename: Xiu-ying
authors.initials: XY
authors.lastname: Pan
authors.forename: Kai-lin
authors.initials: KL
authors.lastname: Xu
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D016207:Cytokines / Q000097:blood; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D005818:Genetic Engineering; D005822:Genetic Vectors; D006086:Graft vs Host Disease / Q000276:immunology*; D016086:Lentivirus; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology*; D014161:Transduction, Genetic; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse