title: Triptolide-conditioned dendritic cells induce allospecific T-cell regulation and prolong renal graft survival.
abstract: BACKGROUND
  Previous studies show that triptolide (TPT), a diterpenoid isolated from the Chinese herb Tripterygium wilfordii Hook.f, inhibits dendritic cell (DCs) maturation. Whether TPT-conditioned DCs (TPT-DCs) may regulate allospecific immune responses remains unclear. In this study, we investigated the effects of TPT on allostimulatory function and phenotype of rat bone marrow-derived DCs (BMDCs).
  
  
  METHODS
  Brown Norway rats BMDCs were cultured with or without TPT and then stimulated with lipopolysaccharide (LPS). IL-10 in supernatants was quantitatively measured, and the cells were analyzed by flow cytometry and used as stimulators in mixed leukocyte reaction in which naive Lewis rat T lymphocytes were used as responders. The tolerogenic potential of TPT-BMDCs was evaluated in vivo in a rat model of MHC fully mismatched kidney transplantation.
  
  
  RESULTS
  After treatment with TPT, BMDCs remained immature with low expression of CD80 and CD86 in the presence of LPS. At low concentrations of TPT (1 and 2.5 nM), BMDCs produced higher levels of IL-10 than the untreated cells (431 and 205.4 pg/ml, respectively, vs. 122.9 pg/ml, p < .05). T cells cocultured with TPT-BMDCs were hyporesponsive in allogeneic mixed lymphocyte reaction. The CD25+foxp3+Treg cell populations increased from 19.9% to 29.7% in the coculture system. Without immunosuppressive therapy, infusion of TPT-BMDCs in recipients before transplantation prolonged rat kidney allograft survival (18.8 ± 1.30 days).
  
  
  CONCLUSIONS
  Our findings demonstrate that TPT inhibits the maturation and allogenicity of BMDCs and promotes the expansion of CD25+foxp3+ regulatory T cells. It suggests that TPT-DCs are potentially useful for preventing kidney transplant rejection.
authors.affiliation: Department of Urology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. zgt6810@yahoo.com.cn
authors.forename: Gutian
authors.initials: G
authors.lastname: Zhang
authors.forename: Junhao
authors.initials: J
authors.lastname: Chen
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Rong
authors.initials: R
authors.lastname: Yang
authors.forename: Hongqian
authors.initials: H
authors.lastname: Guo
authors.forename: Zeyu
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000276:immunology; D002470:Cell Survival; D003713:Dendritic Cells / Q000276:immunology*; D004224:Diterpenes / Q000494:pharmacology*; D004705:Endocytosis / Q000187:drug effects; D004852:Epoxy Compounds / Q000494:pharmacology; D006085:Graft Survival / Q000187:drug effects*; D016753:Interleukin-10 / Q000378:metabolism; D016030:Kidney Transplantation; D008297:Male; D010616:Phenanthrenes / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497966:Cd86 protein, rat; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; D016753:Interleukin-10; C001899:triptolide