A novel technique to explore the functions of bronchial mucosal T cells in chronic obstructive pulmonary disease: application to cytotoxicity and cytokine immunoreactivity

Authors

  • M. W. Lethbridge,

    1. Formerly at King's College London, now at the Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Cambridge, UK,
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  • D. M. Kemeny,

    1. Formerly at King's College London, now Head of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, and
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  • J. C. Ratoff,

    1. King's College London, Department of Asthma, Allergy and Respiratory Science and MRC and Asthma UK Centre for Allergic Mechanisms of Asthma, London, UK
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  • B. J. O'Connor,

    1. King's College London, Department of Asthma, Allergy and Respiratory Science and MRC and Asthma UK Centre for Allergic Mechanisms of Asthma, London, UK
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  • C. M. Hawrylowicz,

    1. King's College London, Department of Asthma, Allergy and Respiratory Science and MRC and Asthma UK Centre for Allergic Mechanisms of Asthma, London, UK
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  • C. J. Corrigan

    Corresponding author
    1. King's College London, Department of Asthma, Allergy and Respiratory Science and MRC and Asthma UK Centre for Allergic Mechanisms of Asthma, London, UK
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  • Funded by King's College London School of Medicine.

C. Corrigan, King's College London, Department of Asthma, Allergy and Respiratory Science, 5th Floor Tower Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
E-mail: chris.corrigan@kcl.ac.uk

Summary

Bronchial mucosal CD8+ cells are implicated in chronic obstructive pulmonary disease (COPD) pathogenesis, but there are few data on their functional properties. We have developed a novel technique to outgrow these cells from COPD patients in sufficient numbers to examine effector functions. Endobronchial biopsies from 15 COPD smokers and 12 ex-smokers, 11 control smokers and 10 non-smokers were cultured with anti-CD3/interleukin (IL)-2 ± IL-15. Outgrown CD3+ T cells were characterized in terms of phenotype (expression of CD4, 8, 25, 28, 69 and 56), cytotoxicity and expression of COPD-related cytokines. Compared with IL-2 alone, additional IL-15 increased the yield and viability of biopsy-derived CD3+ T cells (12–16-day culture without restimulation) without alteration of CD4+/CD8+ ratios or expression of accessory/activation molecules. Biopsy-derived T cells, principally CD8+/CD56+ cells, exhibited statistically significantly greater cytotoxic activity in current or ex-smokers with COPD compared with controls (P < 0·01). Elevated percentages of CD8+ T cells expressed interferon (IFN)-γ, tumour necrosis factor (TNF)-α and IL-13 (P < 0·01) in current COPD smokers compared with all comparison groups. It is possible to perform functional studies on bronchial mucosal T cells in COPD. We demonstrate increased CD8+CD56+ T cell cytotoxic activity and expression of remodelling cytokines in smokers who develop COPD.

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