Distinctive Regulatory T Cells and Altered Cytokine Profile Locally in the Airways of Young Smokers with Normal Lung Function

PLoS One. 2016 Oct 31;11(10):e0164751. doi: 10.1371/journal.pone.0164751. eCollection 2016.

Abstract

Smoking influences the immune system in different ways and, hypothetically, effects on pulmonary effector and regulatory T cells emerge as potentially detrimental. Therefore, we characterized the frequencies and characteristics of CD4+ and CD8+ T cell subsets in the blood and lungs of young tobacco smokers. Bronchoalveolar lavage (BAL) and peripheral blood were obtained from healthy moderate smokers (n = 18; 2-24 pack-years) and never-smokers (n = 15), all with normal lung function. Cells were stimulated ex vivo and key intracellular cytokines (IFNγ, IL-17, IL-10 and TNFα) and transcription factors (Foxp3, T-bet and Helios) were analyzed using flow cytometry. Our results indicate that smoking is associated with a decline in lung IL-17+ CD4+ T cells, increased IFNγ+ CD8+ T cells and these alterations relate to the history of daily cigarette consumption. There is an increased fraction of Foxp3+ regulatory T cells being Helios- in the lungs of smokers. Cytokine production is mainly confined to the Helios- T cells, both in regulatory and effector subsets. Moreover, we detected a decline of Helios+Foxp3- postulated regulatory CD8+ T cells in smokers. These alterations in the immune system are likely to increase risk for infection and may have implications for autoimmune processes initiated in the lungs among tobacco smokers.

MeSH terms

  • Adult
  • Biomarkers
  • Bronchoalveolar Lavage Fluid
  • Cytokines / biosynthesis*
  • Female
  • Humans
  • Immunophenotyping
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lung / metabolism*
  • Male
  • Middle Aged
  • Phenotype
  • Pulmonary Disease, Chronic Obstructive / immunology
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Respiratory Function Tests
  • Respiratory System / metabolism*
  • Smoking*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • Transcription Factors / metabolism
  • Young Adult

Substances

  • Biomarkers
  • Cytokines
  • Transcription Factors

Grants and funding

The study was supported by grants from: The Swedish Heart Lung Foundation; The Swedish Research Council; The Stockholm County Council; Novartis collaborative grant; Torsten and Ragnar Söderberg's Foundation; The King Oscar II Jubilee Foundation; Karolinska Institutet; and The Mats Kleberg Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.