Enhanced effector function of cytotoxic cells in the induced sputum of COPD patients |
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Authors: | Richard A Urbanowicz Jonathan R Lamb Ian Todd Jonathan M Corne Lucy C Fairclough |
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Institution: | 1.COPD Research Group, Nottingham Respiratory Biomedical Research Unit, The University of Nottingham, NG7 2UH, UK;2.Immunology and Infection Section, Division of Cell and Molecular Biology, Faculty of Natural Sciences, Imperial College London, South Kensington, London, SW7 9AZ, UK;3.Department of Respiratory Medicine, Nottingham University Hospitals, NG7 2UH, UK |
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Abstract: | BackgroundWe have previously shown that NK (CD56+CD3-) and NKT-like (CD56+CD3+) cells are reduced in both numbers and cytotoxicity in peripheral blood. The aim of the present study was to investigate their numbers and function within induced sputum.MethodsInduced sputum cell numbers and intracellular granzyme B and perforin were analysed by flow cytometry. Immunomagnetically selected CD56+ cells (NK and NKT-like cells) were used in an LDH release assay to determine cytotoxicity.ResultsThe proportion of NK cells and NKT-like cells in smokers with COPD (COPD subjects) was significantly higher (12.7% and 3%, respectively) than in healthy smokers (smokers) (5.7%, p < 0.01; 1%, p < 0.001) and non-smoking healthy subjects (HNS) (4.2%, p < 0.001; 0.8%, p < 0.01). The proportions of NK cells and NKT-like cells expressing both perforin and granzyme B were also significantly higher in COPD subjects compared to smokers and HNS. CD56+ cells from COPD subjects were significantly more cytotoxic (1414 biological lytic activity) than those from smokers (142.5; p < 0.01) and HNS (3.8; p < 0.001) and were inversely correlated to FEV1. (r = -0.75; p = 0.0098).ConclusionWe have shown an increased proportion of NK and NKT-like cells in the induced sputum of COPD subjects and have demonstrated that these cells are significantly more cytotoxic in COPD subjects than smokers and HNS. |
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