University of Oulu

Forsslund H, Yang M, Mikko M, Karimi R, Nyrén S, Engvall B, Grunewald J, Merikallio H, Kaarteenaho R, Wahlström J, Wheelock ÅM, Sköld CM. Gender differences in the T-cell profiles of the airways in COPD patients associated with clinical phenotypes. International Journal of COPD 2017:12 35–48.

Gender differences in the T-cell profiles of the airways in COPD patients associated with clinical phenotypes

Saved in:
Author: Forsslund, Helena1; Yang, Mingxing1; Mikko, Mikael1;
Organizations: 1Department of Medicine Solna and Centre for Molecular Medicine, Respiratory Medicine Unit
2Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden
3Respiratory Research Unit and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland
4Unit of Medicine and Clinical Research, Pulmonary Division, University of Eastern Finland
5Center for Medicine and Clinical Research, Division of Respiratory Medicine, Kuopio University Hospital, Kuopio, Finland
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 2.6 MB)
Persistent link:
Language: English
Published: Dove Medical Press, 2017
Publish Date: 2017-03-30


T lymphocytes are believed to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). How T cells are recruited to the lungs and contribute to the inflammatory process is largely unknown. COPD is a heterogeneous disease, and discriminating disease phenotypes based on distinct molecular and cellular pathways may provide new approaches for individualized diagnosis and therapies. Bronchoalveolar lavage (BAL) and blood samples were obtained from 40 never-smokers, 40 smokers with normal lung function, and 38 COPD patients. T-cell chemokine receptor expression was analyzed with flow cytometry, and soluble BAL cytokines and chemokines were measured using a cytokine multiplex assay. Correlations with gender and clinical characteristics including lung imaging were investigated using multivariate modeling. Th1/Tc1- and Th2/Tc2-associated soluble analytes and T-cell chemokine receptors were analyzed as cumulative Th1/Tc1 and Th2/Tc2 immune responses. A higher expression of chemokine receptor CCR5 on CD8⁺ T cells in BAL and higher percentage of CXCR3⁺CD8⁺ T cells in blood was found in female smokers with COPD compared to those without COPD. CCR5 expression on CD4⁺ and CD8⁺ T cells was lower in BAL from male smokers with COPD compared to those without COPD. Among female smokers with COPD, Th1/Tc1 immune response was linked to BAL macrophage numbers and goblet cell density, and Th2/Tc2 response was associated with the measures of emphysema on high-resolution computed tomography. The highly gender-dependent T-cell profile in COPD indicates different links between cellular events and clinical manifestations in females compared to males. Our findings may reveal mechanisms of importance for the difference in clinical course in female COPD patients compared to males.

see all

Series: International journal of chronic obstructive pulmonary disease
ISSN: 1176-9106
ISSN-E: 1178-2005
ISSN-L: 1176-9106
Volume: 12
Pages: 35 - 48
DOI: 10.2147/COPD.S113625
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: This study was supported by grants from the Swedish Heart-Lung Foundation, the King Oscar II Jubilee Foundation, the Mats Kleberg Foundation, King Gustaf V’s and Queen Victoria’s Freemasons’ Foundation, the Hesselmans Foundation, Sandoz A/S, Swedish Governmental Agency for Innovation Systems (VINNOVA), the Swedish Foundation for Strategic Research (SSF), European Union (EU) Fp6 Marie Curie International Reintegration Grant (IRF), the Foundation of the Finnish Anti-Tuberculosis Association, the Swedish Research Council (VR), the Stockholm County Council (ALF project), and Karolinska Institutet.
Copyright information: © 2017 Forsslund et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (