title: Methylprednisolone inhibits activated CD4+ T cell survival promoted by toll-like receptor ligands.
abstract: BACKGROUND
  Methylprednisolone (MP) can affect the survival of CD4+ T lymphocytes and plays an important role in adaptive immune responses; however, its mechanism of action is not clear. Recent studies have shown that toll-like receptors (TLRs) on CD4+ T cells can directly modulate adaptive immune responses by affecting the survival and proliferation of activated CD4+ T cells. This study aimed to investigate the relationship between MP, TLRs and activated CD4+ T cells.
  
  
  METHODS
  We separated and purified CD4+ T cells from mice, activated them in vitro, and co-cultured them with TLR ligands, MP or inhibitors of nuclear factor-kappa B (NF-kappaB) and activator protein 1 (AP-1). We then assessed CD4+ T cell survival and proliferation and the expression of NF-kappaB and AP-1.
  
  
  RESULTS
  Activated CD4+ T cells showed increased TLR-3 and TLR-9 mRNA expression, but polyinosinic-polycytidylic acid (poly I:C) and MP had no effect on the expression of these mRNAs. Still, poly I:C and CpG oligodeoxynucleotides (CpG DNA) increased the survival of activated CD4+ T cells, whereas MP reduced the survival of activated CD4+ T cells and could inhibit the survival effects of poly I:C and CpG DNA. The NF-kappaB essential modifier-binding domain (NBD) inhibited the survival of activated CD4+ T cells induced by poly I:C and CpG DNA, but the AP-1 inhibitor crucumin did not have the same effect. The increased expression of NF-kappaB induced by poly I:C and CpG DNA in activated CD4+ T cells could be inhibited by MP, but the same was not true for the increased expression of AP-1 induced by poly I:C and CpG DNA. Finally, the proliferation of activated CD4+ T cells was not affected by poly I:C or MP.
  
  
  CONCLUSIONS
  The survival of activated CD4+ T cells is promoted by TLR ligands, but this effect is inhibited by MP.
authors.affiliation: Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical University, China.
authors.forename: You-Sheng
authors.initials: YS
authors.lastname: Lu
authors.forename: Li-Yong
authors.initials: LY
authors.lastname: Pu
authors.forename: Xiang-Cheng
authors.initials: XC
authors.lastname: Li
authors.forename: Xue-Hao
authors.initials: XH
authors.lastname: Wang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D008024:Ligands; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D016328:NF-kappa B / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D008024:Ligands; D016328:NF-kappa B; C519703:TLR3 protein, mouse; C495370:Tlr9 protein, mouse; D051196:Toll-Like Receptor 3; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D018808:Transcription Factor AP-1; D011070:Poly I-C; D008775:Methylprednisolone