Expansion of CD4+CD25+ helper T cells without regulatory function in smoking and COPD

Respir Res. 2011 Jun 8;12(1):74. doi: 10.1186/1465-9921-12-74.


Background: Regulatory T cells have been implicated in the pathogenesis of COPD by the increased expression of CD25 on helper T cells along with enhanced intracellular expression of FoxP3 and low/absent CD127 expression on the cell surface.

Method: Regulatory T cells were investigated in BALF from nine COPD subjects and compared to fourteen smokers with normal lung function and nine never-smokers.

Results: In smokers with normal lung function, the expression of CD25+CD4+ was increased, whereas the proportions of FoxP3+ and CD127+ were unchanged compared to never-smokers. Among CD4+ cells expressing high levels of CD25, the proportion of FoxP3+ cells was decreased and the percentage of CD127+ was increased in smokers with normal lung function. CD4+CD25+ cells with low/absent CD127 expression were increased in smokers with normal lung function, but not in COPD, when compared to never smokers.

Conclusion: The reduction of FoxP3 expression in BALF from smokers with normal lung function indicates that the increase in CD25 expression is not associated with the expansion of regulatory T cells. Instead, the high CD127 and low FoxP3 expressions implicate a predominantly non-regulatory CD25+ helper T-cell population in smokers and stable COPD. Therefore, we suggest a smoking-induced expansion of predominantly activated airway helper T cells that seem to persist after COPD development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bronchoalveolar Lavage Fluid / immunology
  • Case-Control Studies
  • Cell Proliferation*
  • Female
  • Flow Cytometry
  • Forced Expiratory Volume
  • Forkhead Transcription Factors / analysis
  • Humans
  • Interleukin-2 Receptor alpha Subunit / analysis*
  • Interleukin-7 Receptor alpha Subunit / analysis
  • Lung / physiopathology
  • Lymphocyte Activation*
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / immunology*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Smoking / adverse effects
  • Smoking / immunology*
  • Spirometry
  • Sweden
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Vital Capacity


  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-7 Receptor alpha Subunit