Increased bronchial density of CD25+Foxp3+ regulatory T cells in occupational asthma: relationship to current smoking

Scand J Immunol. 2013 May;77(5):398-404. doi: 10.1111/sji.12035.

Abstract

To identify activated T cell subset in the asthmatic bronchia, we developed a triple-colour immunohistofluorescence labelling technique on cryo-section to discriminate activated CD4+CD25+ T cells, (effector T cells) from Foxp3+ regulatory T cells (Treg). Additional coexpression of activation and proliferation markers was also examined in situ. Bronchial biopsies were taken from 20 aluminium potroom workers (12 smokers) with asthma (>12% reversibility), 15 non-asthmatic potroom workers (7 smokers) and 10 non-smoking, non-exposed controls. Non-smoking asthmatics had significantly higher subepithelial density of both Tregs, effector T cells, activated (HLA-DR+) CD8+ and activated CD4+ T cells. Moreover, both Tregs, effector T cells and CD8+ T cells proliferated in the non-smoking asthmatics, only. Although smoking asthmatics had no asthma-associated increase in bronchial T cell, both had a significantly increase in effector T cell to Treg ratios. The significantly increased bronchial density of Tregs, effector T cells, proliferative T cells and activated CD8+ T cells in non-smoking asthmatics clearly showed that both the effector T cells and the inhibitory Treg system were activated in asthma.

MeSH terms

  • Adult
  • Asthma, Occupational / immunology*
  • Asthma, Occupational / metabolism
  • Bronchi / immunology*
  • Bronchi / pathology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Proliferation
  • Forkhead Transcription Factors / immunology
  • Forkhead Transcription Factors / metabolism
  • HLA-DR Antigens / immunology
  • HLA-DR Antigens / metabolism
  • Humans
  • Immunohistochemistry / methods
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Lymphocyte Activation / immunology
  • Lymphocyte Count
  • Microscopy, Fluorescence
  • Middle Aged
  • Smoking / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Young Adult

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • HLA-DR Antigens
  • Interleukin-2 Receptor alpha Subunit