Higher Bcl-2 levels decrease staphylococcal superantigen-induced apoptosis of CD4+ T cells in atopic dermatitis
Journal
Allergy: European Journal of Allergy and Clinical Immunology
Journal Volume
62
Journal Issue
5
Pages
520-526
Date Issued
2007
Author(s)
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 (TCRVβ3+, Vβ12+, and Vβ17 +) 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. ? 2007 The Authors.
SDGs
Other Subjects
bacterial antigen; caspase 3; interleukin 4; messenger RNA; neutralizing antibody; protein bcl 2; recombinant interleukin 4; Staphylococcus enterotoxin B; adult; allergy; apoptosis; article; atopic dermatitis; CD4+ T lymphocyte; clinical article; enzyme activation; female; flow cytometry; human; immunofluorescence; male; priority journal; reverse transcription polymerase chain reaction; skin inflammation; staining; upregulation; Adolescent; Adult; Antigens, Bacterial; Apoptosis; CD4-Positive T-Lymphocytes; Cells, Cultured; Cross-Sectional Studies; Dermatitis, Atopic; Female; Humans; Male; Proto-Oncogene Proteins c-bcl-2; Staphylococcus; Superantigens
Type
journal article