title: Bortezomib modulates regulatory T cell subpopulations in the process of acute graft-versus-host disease.
abstract: BACKGROUND
  Acute graft-versus-host disease (aGVHD) combines the wide application of allogeneic bone marrow transplantation (allo-BMT). Recent studies indicate that it is possible to reduce the incidence and severity of aGVHD by using bortezomib. In this study, we explored the changes of T cell subsets after allo-BMT with bortezomib, in order to elucidate the mechanism by which bortezomib attenuates aGVHD.
  
  
  METHODS
  Following a single dose of lethal irradiation (TBI, 0.7 Gy/minutes, 8.0 Gy), BALB/c mice were injected with 2 x 10(7) C57BL/6 nucleated BM cells plus 1 x 10(7) splenocytes with or without bortezomib at 1.0 mg/kg. The ratio of CD4+CD25+ Foxp3+ regulatory T cells (Treg) was examined by flow cytometry, and the cytokine levels of IL-2 (Th1) and IL-4 (Th2) were detected by ELISA. Bivariate correlation analysis was carried out to evaluate changes of the Th1 and Th2 cytokines related to the changes of Treg.
  
  
  RESULTS
  Bortezomib remarkably reduced aGVHD severity and prolonged the survival time. Along with bortezomib injection, the ratio of Treg was significantly increased and IL-2 level was decreased but IL-4 level was increased. Bivariate correlation analysis results evaluated the correlation between the increment of Treg and changes of Th1 and Th2 cytokines.
  
  
  CONCLUSIONS
  Bortezomib may exert its effect by triggering the generation of Treg which might regulate the imbalance of Th1/Th2 during aGVHD.
authors.affiliation: Department of Haematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Weng
authors.forename: Peilong
authors.initials: P
authors.lastname: Lai
authors.forename: Meikun
authors.initials: M
authors.lastname: Lv
authors.forename: Shaoze
authors.initials: S
authors.lastname: Lin
authors.forename: Wei
authors.initials: W
authors.lastname: Ling
authors.forename: Suxia
authors.initials: S
authors.lastname: Geng
authors.forename: Chenwei
authors.initials: C
authors.lastname: Luo
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Du
mesh_terms: D000208:Acute Disease; D000818:Animals; D016026:Bone Marrow Transplantation; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011719:Pyrazines / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib