title: Experimental study of the mechanism of tolerance induction in dexamethasone-treated dendritic cells.
abstract: BACKGROUND
  The aim of this study was to investigate the mechanisms underlying tolerance induction of dexamethasone (Dex)-treated dendritic cells (DCs).
  
  
  METHODS
  Well-grown DC2.4 cells were randomly assigned to receive control, 50 µg/L, 100 µg/L, or 200 µg/L of dexamethasone and then were cultured for 6 days. The expressions of CD80, CD86, galectin-9, and PD-L1 on the surface of DC2.4 cells were analyzed with flow cytometry and the level of IL-12 secreted by DC2.4 cells was determined by ELISA. The stimulating activity of DC2.4 cells on allogeneic T cells was assessed with mixed lymphocyte reaction. Dexamethasone-treated DC2.4 cells were co-cultured with allogeneic splenic lymphocytes and the Foxp3 expression in naive T lymphocytes was determined with flow cytometry.
  
  
  RESULTS
  Compared with the control group, the expressions of CD80, CD86, galectin-9, and PD-L1 on the surface of DC2.4 cells exposed to different doses of dexamethasone showed no significant changes; however, dexamethasone treatment significantly reduced IL-12 secretion and inhibited DC2.4's stimulation on the proliferation of allogeneic T lymphocytes. Moreover, dexamethasone-treated DC2.4 cells effectively promoted FOXP3 expression in naive T lymphocytes.
  
  
  CONCLUSIONS
  DC2.4 is a stable cell line with high expressions of CD80, CD86, and PD-L1. Dexamethasone does not significantly change the cell phenotype of DC2.4 cells, but inhibits the secretion of IL-12 cytokine and attenuates DC2.4's stimulation of the proliferation of allogeneic T cells. Dexamethasone-treated DC2.4 cells also effectively promote FOXP3 expression in naive T lymphocytes.
authors.affiliation: Department of Ophthalmology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yu-bo
authors.initials: YB
authors.lastname: Gong
authors.forename: Yi-fei
authors.initials: YF
authors.lastname: Huang
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Gen-cheng
authors.initials: GC
authors.lastname: Han
authors.forename: Yu-rong
authors.initials: YR
authors.lastname: Li
authors.forename: Da-jiang
authors.initials: DJ
authors.lastname: Wang
authors.forename: Gai-ping
authors.initials: GP
authors.lastname: Du
authors.forename: Ji-feng
authors.initials: JF
authors.lastname: Yu
authors.forename: Jing
authors.initials: J
authors.lastname: Song
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D003907:Dexamethasone / Q000494:pharmacology*; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D037161:Galectins / Q000378:metabolism; D007108:Immune Tolerance / Q000187:drug effects*; D018664:Interleukin-12 / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D037161:Galectins; C508186:galectin 9, mouse; D018664:Interleukin-12; D003907:Dexamethasone