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Impaired CTLA-4 responses in COPD are associated with systemic inflammation

Cellular & Molecular Immunology volume 11, pages 606–608 (2014)Cite this article

Systemic inflammation is a feature of chronic obstructive pulmonary disease (COPD). Defects in T cell-mediated anti-inflammatory pathways such as cytotoxic T lymphocyte antigen-4 (CTLA-4) may promote damaging inflammation. This study provides novel data implicating the impaired induction of an anti-inflammatory molecule, CTLA-4 in the elevated inflammation observed in COPD patients. Low induction of CTLA-4 in COPD patients paralleled increased markers of systemic inflammation ex vivo and increased T-cell responses to a bacterial superantigen, staphylococcal enterotoxin-B (SEB) in vitro. This mechanism may explain the increased inflammation in COPD patients.

COPD is a leading cause of mortality and morbidity worldwide, affecting mostly smokers and the elderly. COPD is characterized by irreversible inflammation and destruction of lung tissue, leading to airflow obstruction.1 It has been recognized as a multisystemic inflammatory disorder associated with cachexia, vascular and ischaemic heart disease.2 Systemic biomarkers of chronic inflammation such as soluble tumour-necrosis factor receptor (sTNFR) and the activation of T cells (HLA-DR expression) are elevated in this condition.3,4

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Acknowledgements

This work was supported by an Ada Bartholomew Grant from the Faculty of Medicine, Dentistry and Health Science, University of Western Australia and a Young Investigator Grant from the Medical Research Foundation of Royal Perth Hospital. We thank Dr Neil Misso for editorial support, the staff at the COPD Linkage Clinic, Ms Elizabeth Hyde and Ms Leah Christie for patient recruitment, and the patients and controls who volunteered for this study.

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Authors and Affiliations

  1. Centre for Asthma, Allergy and Respiratory Research, Lung Institute of Western Australia, Nedlands, Australia

    Dino BA Tan, Philip J Thompson & Yuben P Moodley

  2. School of Medicine and Pharmacology, Nedlands, Australia

    Dino BA Tan & Yuben P Moodley

  3. School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Australia

    Sonia Fernandez, Patricia Price & Martyn A French

  4. Department of Clinical Immunology, Perth, Australia

    Martyn A French

  5. Department of Respiratory and Sleep Medicine, Royal Perth Hospital, Perth, Australia

    Yuben P Moodley

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  1. Dino BA Tan
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  2. Sonia Fernandez
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  3. Patricia Price
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  4. Martyn A French
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  5. Philip J Thompson
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  6. Yuben P Moodley
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Correspondence to Dino BA Tan.

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Supplementary Information accompanies the paper on Cellular & Molecular Immunology's website. (http://www.nature.com/cmi).

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Tan, D., Fernandez, S., Price, P. et al. Impaired CTLA-4 responses in COPD are associated with systemic inflammation. Cell Mol Immunol 11, 606–608 (2014). https://doi.org/10.1038/cmi.2014.20

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