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Respiratory Research
Published in: Respiratory Research 1/2009

Open Access 01-12-2009 | Research

Altered effector function of peripheral cytotoxic cells in COPD

Authors: Richard A Urbanowicz, Jonathan R Lamb, Ian Todd, Jonathan M Corne, Lucy C Fairclough

Published in: Respiratory Research | Issue 1/2009

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Abstract

Background

There is mounting evidence that perforin and granzymes are important mediators in the lung destruction seen in COPD. We investigated the characteristics of the three main perforin and granzyme containing peripheral cells, namely CD8+ T lymphocytes, natural killer (NK; CD56+CD3-) cells and NKT-like (CD56+CD3+) cells.

Methods

Peripheral blood mononuclear cells (PBMCs) were isolated and cell numbers and intracellular granzyme B and perforin were analysed by flow cytometry. Immunomagnetically selected CD8+ T lymphocytes, NK (CD56+CD3-) and NKT-like (CD56+CD3+) cells were used in an LDH release assay to determine cytotoxicity and cytotoxic mechanisms were investigated by blocking perforin and granzyme B with relevant antibodies.

Results

The proportion of peripheral blood NKT-like (CD56+CD3+) cells in smokers with COPD (COPD subjects) was significantly lower (0.6%) than in healthy smokers (smokers) (2.8%, p < 0.001) and non-smoking healthy participants (HNS) (3.3%, p < 0.001). NK (CD56+CD3-) cells from COPD subjects were significantly less cytotoxic than in smokers (16.8% vs 51.9% specific lysis, p < 0.001) as were NKT-like (CD56+CD3+) cells (16.7% vs 52.4% specific lysis, p < 0.001). Both cell types had lower proportions expressing both perforin and granzyme B. Blocking the action of perforin and granzyme B reduced the cytotoxic activity of NK (CD56+CD3-) and NKT-like (CD56+CD3+) cells from smokers and HNS.

Conclusion

In this study, we show that the relative numbers of peripheral blood NK (CD56+CD3-) and NKT-like (CD56+CD3+) cells in COPD subjects are reduced and that their cytotoxic effector function is defective.
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Metadata
Title
Altered effector function of peripheral cytotoxic cells in COPD
Authors
Richard A Urbanowicz
Jonathan R Lamb
Ian Todd
Jonathan M Corne
Lucy C Fairclough
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2009
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-10-53

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