title: Higher Bcl-2 levels decrease staphylococcal superantigen-induced apoptosis of CD4+ T cells in atopic dermatitis.
abstract: BACKGROUND
  Staphylococcal superantigens (SsAgs) contribute to the persistence of allergic skin inflammation in atopic dermatitis (AD). The aims of this study were to (1) determine whether there are differences between AD patients and healthy subjects in SsAg-induced caspase-3 activation and SsAg-induced changes of anti-apoptotic protein Bcl-2 and Bcl-2 mRNA levels of CD4+ T cells; (2) investigate the effect of interleukin (IL)-4 on SsAg-induced caspase-3 activation and SsAg-induced changes of Bcl-2 and Bcl-2 mRNA levels of CD4+ T cells.
  
  
  METHODS
  Using immunofluorescence staining followed by flow cytometric analysis and real-time PCR, we analyzed peripheral blood mononuclear cells with or without staphylococcal enterotoxin B (SEB) stimulation in the presence or absence of recombinant IL-4 or anti-IL-4 neutralizing antibodies in 16 AD patients and 14 healthy subjects.
  
  
  RESULTS
  SEB-reactive (TCRVbeta3+, Vbeta12+, and Vbeta17+) CD4+ T cells from AD patients were more resistant to SEB-induced caspase-3 activation and SEB-induced decrease of Bcl-2 and Bcl-2 mRNA than those from healthy subjects. Exogenously added IL-4 inhibited SEB-induced caspase-3 activation and SEB-induced decrease of Bcl-2 and Bcl-2 mRNA in SEB-reactive CD4+ T cells from healthy subjects. Inhibition of endogenous IL-4 by using anti-IL-4 neutralizing antibodies up-regulated SEB-induced caspase-3 activation and SEB-induced decrease of Bcl-2 and Bcl-2 mRNA in SEB-reactive CD4+ T cells from AD patients.
  
  
  CONCLUSIONS
  Following SsAg stimulation, IL-4 produced by T cells in AD patients down-regulates SsAg-induced caspase-3 activation and apoptosis of CD4+ T cells through inhibiting the decrease of Bcl-2. This may impair deletion of SsAg-activated T cells and resolution of allergic skin inflammation.
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Y T
authors.initials: YT
authors.lastname: Lin
authors.forename: C T
authors.initials: CT
authors.lastname: Wang
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.forename: C Y
authors.initials: CY
authors.lastname: Chu
authors.forename: W C
authors.initials: WC
authors.lastname: Tsao
authors.forename: Y H
authors.initials: YH
authors.lastname: Yang
authors.forename: B L
authors.initials: BL
authors.lastname: Chiang
mesh_terms: D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000382:microbiology; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000378:metabolism*; D013210:Staphylococcus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology* / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D019253:Proto-Oncogene Proteins c-bcl-2; D018089:Superantigens