Enhanced effector function of cytotoxic cells in the induced sputum of COPD patients.
BACKGROUND
We 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.


METHODS
Induced 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.


RESULTS
The 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).


CONCLUSIONS
We 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.
Urbanowicz
Richard A
RA
COPD Research Group, Nottingham Respiratory Biomedical Research Unit, The University of Nottingham, UK.
Lamb
Jonathan R
JR
Todd
Ian
I
Corne
Jonathan M
JM
Fairclough
Lucy C
LC
D000328:Adult; D000368:Aged; D017252:CD3 Complex / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D005541:Forced Expiratory Volume; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D018189:Immunomagnetic Separation; D039041:Integrin alpha4beta1 / Q000378:metabolism; D020014:K562 Cells; D008168:Lung / Q000276:immunology* / Q000503:physiopathology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology*; D054353:Perforin / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000503:physiopathology; D054367:Receptors, CXCR3 / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects; D013183:Sputum / Q000166:cytology / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014797:Vital Capacity
D017252:CD3 Complex; D019002:CD56 Antigen; C515187:CXCR3 protein, human; D039041:Integrin alpha4beta1; D054367:Receptors, CXCR3; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes