Skin-homing CD4+ Foxp3+ T cells exert Th2-like function after staphylococcal superantigen stimulation in atopic dermatitis patients

Clin Exp Allergy. 2011 Apr;41(4):516-25. doi: 10.1111/j.1365-2222.2010.03681.x. Epub 2011 Jan 24.

Abstract

Background: The effect of staphylococcal superantigens (SsAgs) on cutaneous lymphocyte-associated antigen (CLA)(+) CD4(+) Foxp3(+) T cells of atopic dermatitis (AD) patients is unknown.

Objective: To compare the effects of SsAgs on the ratio, function, and apoptosis of CCR6(+) subtype and CCR6(-) subtype of CLA(+) CD4(+) Foxp3(+) T cells among AD patients, asthma/allergic rhinitis (AR) patients without AD, and healthy subjects.

Methods: Using immunofluorescence staining followed by flow cytometric analysis, we analysed peripheral blood mononuclear cells cultured with or without staphylococcal enterotoxin B (SEB) stimulation in 20 AD patients, 20 asthma/AR patients without AD, and 20 healthy subjects.

Results: SEB decreased CCR6(+) /CCR6(-) ratio in CLA(+) CD4(+) Foxp3(+) T cells from AD patients and increased CCR6(+) /CCR6(-) ratio in those from healthy subjects. SEB induced the production of type 2 T helper cell (Th2) cytokine interleukin (IL)-5 in CCR6(-) subtype and anti-inflammatory cytokine IL-10 in CCR6(+) subtype of CLA(+) CD4(+) Foxp3(+) T cells. CLA(+) CD4(+) Foxp3(+) T cells from AD patients produced more IL-5 and less IL-10 after SEB stimulation than those from healthy subjects. CCR6(-) subtype of CLA(+) CD4(+) Foxp3(+) T cells from AD patients and CCR6(+) subtype of those cells from healthy subjects were more resistant to SEB-induced caspase-3 activation than the other subtype and those from other subjects.

Conclusions and clinical relevance: Despite a phenotype of regulatory T cells, skin-homing CD4(+) Foxp3(+) T cells of AD patients exert effector Th2-like function after SsAgs stimulation, which may aggravate allergic skin inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • Cell Separation
  • Cross-Sectional Studies
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Dermatitis, Atopic / immunology*
  • Enterotoxins / immunology*
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Forkhead Transcription Factors / immunology
  • Humans
  • Male
  • Membrane Glycoproteins / immunology
  • Skin / cytology
  • Skin / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Th2 Cells / immunology

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • CTAGE1 protein, human
  • Cytokines
  • Enterotoxins
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Membrane Glycoproteins
  • enterotoxin B, staphylococcal