title: Distinctive Regulatory T Cells and Altered Cytokine Profile Locally in the Airways of Young Smokers with Normal Lung Function.
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.
authors: Respiratory Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.|Center for Molecular Medicine (CMM), Karolinska Institutet, Stockholm, Sweden.
authors: Mahyar
authors: M
authors: Ostadkarampour
authors: Rheumatology Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.|Center for Molecular Medicine (CMM), Karolinska Institutet, Stockholm, Sweden.
authors: Malin
authors: M
authors: Müller
authors: Respiratory Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.|Center for Molecular Medicine (CMM), Karolinska Institutet, Stockholm, Sweden.
authors: Johan
authors: J
authors: Öckinger
authors: Respiratory Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.|Karolinska University Hospital, Stockholm, Sweden.
authors: Susanna
authors: S
authors: Kullberg
authors: Unit for Lung and Airway Research, Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, Sweden.|Karolinska University Hospital, Stockholm, Sweden.
authors: Anders
authors: A
authors: Lindén
authors: Respiratory Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.|Center for Molecular Medicine (CMM), Karolinska Institutet, Stockholm, Sweden.|Karolinska University Hospital, Stockholm, Sweden.
authors: Anders
authors: A
authors: Eklund
authors: Respiratory Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.|Center for Molecular Medicine (CMM), Karolinska Institutet, Stockholm, Sweden.|Karolinska University Hospital, Stockholm, Sweden.
authors: Johan
authors: J
authors: Grunewald
authors: Respiratory Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.|Center for Molecular Medicine (CMM), Karolinska Institutet, Stockholm, Sweden.
authors: Jan
authors: J
authors: Wahlström
mesh_terms: D000328:Adult; D015415:Biomarkers; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology / Q000378:metabolism; D012129:Respiratory Function Tests; D012137:Respiratory System / Q000378:metabolism*; D012907:Smoking; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D014157:Transcription Factors