title: [Preferential induction of apoptosis in regulatory T cells by tributyltin: possible involvement in the exacerbation of allergic diseases].
abstract: OBJECTIVE
  Tributyltin (TBT) has been recognized as a particularly important pollutant. Human exposure to TBT persists via consumption of TBT-containing meat and fish products. Although it is well known that high-dose TBT exerts immunotoxic effects such as thymic atrophy, the effect of low-dose TBT exposure on immune responses remains elusive. Our previous studies demonstrated that TBT at environmentally relevant doses promoted T helper (Th)2 polarization via enhancement of Th2 differentiation and preferential induction of apoptosis in Th1, which is associated with the exacerbation of Th2-driven allergic airway inflammation. In the present study, we explored the possibility that TBT might preferentially induce apoptosis in Foxp3(+) regulatory T cells (Treg), which play an indisputable role in the negative regulation of immune responses.
  
  
  METHODS
  We established several independent Treg and Th2 clones and their susceptibilities to TBT-induced apoptosis were examined. To examine whether the susceptibility to TBT-induced apoptosis may be due to the level of glutathione (GSH), we measured the basal GSH levels in Treg and Th2 clones. Intracellular GSH level was measured using high-performance liquid chromatography (HPLC) with a gold electrode.
  
  
  RESULTS
  We show that TBT preferentially induces apoptosis in Treg clones rather than in Th2 clones. The basal levels of GSH in Treg clones were significantly lower than those in Th2 clones.
  
  
  CONCLUSIONS
  The increased susceptibility of Treg clones to TBT-induced apoptosis appeared to result from lower GSH levels in Treg clones, which may detoxify the reactive oxygen species (ROS) induced by TBT treatment. Our results suggest that the preferential induction of apoptosis in Treg over Th2 contributes to the exacerbation of Th2-driven allergic diseases by TBT.
authors.affiliation: Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie, Japan. t-saeko@doc.medic.mie-u.ac.jp
authors.forename: Saeko
authors.initials: S
authors.lastname: Tada-Oikawa
authors.forename: Mariko
authors.initials: M
authors.lastname: Murata
authors.forename: Takuma
authors.initials: T
authors.lastname: Kato
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002999:Clone Cells; D004785:Environmental Pollutants / Q000009:adverse effects*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology*; D051379:Mice; D008815:Mice, Inbred Strains; D017382:Reactive Oxygen Species / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014220:Trialkyltin Compounds / Q000009:adverse effects*
chemical_list: D004785:Environmental Pollutants; D017382:Reactive Oxygen Species; D014220:Trialkyltin Compounds; C011559:tributyltin; D005978:Glutathione