BACKGROUND AND OBJECTIVE: Natural killer (NK) and natural killer T (NKT)-like cells represent a small but important proportion of effector lymphocytes that we have previously shown to be major sources of pro-inflammatory cytokines and granzymes. We hypothesized that these cells would be increased in the airway in chronic obstructive pulmonary disease (COPD), accompanied by reduced expression of the inhibitory receptor CD94 (Kp43) and increased expression of cytotoxic mediators granzyme B and perforin. METHODS: We measured NK and NKT-like cells and their expression of CD94 in the blood of COPD patients (n = 71; 30 current and 41 ex-smokers), smokers (16) and healthy controls (25), and bronchoalveolar lavage fluid (BALF) from a cohort of subjects (19 controls, 12 smokers, 33 COPD). Activation was assessed by measuring CD69 in blood and the cytotoxic potential of NK cells by measuring granzymes A and B, and using a cytotoxicity assay in blood and BALF. RESULTS: In blood in COPD, there were no significant changes in the proportion of NK or NKT-like cells or expression of granzyme A or NK cytotoxic potential versus controls. There was, however, increased expression of granzyme B and decreased expression of CD94 by both cell types versus controls. The proportion of NK and NKT-like cells were increased in BALF in COPD, associated with increased NK cytotoxicity, increased expression of granzyme B and decreased expression of the inhibitory receptor CD94 by both cell types. CONCLUSIONS: Treatment strategies that target NK and NKT-like cells, their cytotoxicity and production of inflammatory mediators in the airway may improve COPD morbidity.
BACKGROUND AND OBJECTIVE: Natural killer (NK) and natural killer T (NKT)-like cells represent a small but important proportion of effector lymphocytes that we have previously shown to be major sources of pro-inflammatory cytokines and granzymes. We hypothesized that these cells would be increased in the airway in chronic obstructive pulmonary disease (COPD), accompanied by reduced expression of the inhibitory receptor CD94 (Kp43) and increased expression of cytotoxic mediators granzyme B and perforin. METHODS: We measured NK and NKT-like cells and their expression of CD94 in the blood of COPD patients (n = 71; 30 current and 41 ex-smokers), smokers (16) and healthy controls (25), and bronchoalveolar lavage fluid (BALF) from a cohort of subjects (19 controls, 12 smokers, 33 COPD). Activation was assessed by measuring CD69 in blood and the cytotoxic potential of NK cells by measuring granzymes A and B, and using a cytotoxicity assay in blood and BALF. RESULTS: In blood in COPD, there were no significant changes in the proportion of NK or NKT-like cells or expression of granzyme A or NK cytotoxic potential versus controls. There was, however, increased expression of granzyme B and decreased expression of CD94 by both cell types versus controls. The proportion of NK and NKT-like cells were increased in BALF in COPD, associated with increased NK cytotoxicity, increased expression of granzyme B and decreased expression of the inhibitory receptor CD94 by both cell types. CONCLUSIONS: Treatment strategies that target NK and NKT-like cells, their cytotoxicity and production of inflammatory mediators in the airway may improve COPD morbidity.
Authors: Donna K Finch; Valerie R Stolberg; John Ferguson; Henrih Alikaj; Mohamed R Kady; Bradley W Richmond; Vasiliy V Polosukhin; Timothy S Blackwell; Lisa McCloskey; Jeffrey L Curtis; Christine M Freeman Journal: Am J Respir Crit Care Med Date: 2018-11-01 Impact factor: 21.405
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Authors: G Hodge; J Barnawi; C Jurisevic; D Moffat; M Holmes; P N Reynolds; H Jersmann; S Hodge Journal: Clin Exp Immunol Date: 2014-10 Impact factor: 4.330
Authors: M Pichavant; G Rémy; S Bekaert; O Le Rouzic; G Kervoaze; E Vilain; N Just; I Tillie-Leblond; F Trottein; D Cataldo; P Gosset Journal: Mucosal Immunol Date: 2013-10-30 Impact factor: 7.313
Authors: Christine M Freeman; Valerie R Stolberg; Sean Crudgington; Fernando J Martinez; MeiLan K Han; Stephen W Chensue; Douglas A Arenberg; Catherine A Meldrum; Lisa McCloskey; Jeffrey L Curtis Journal: PLoS One Date: 2014-07-31 Impact factor: 3.240
Authors: Jarrett D Morrow; Weiliang Qiu; Divya Chhabra; Stephen I Rennard; Paula Belloni; Anton Belousov; Sreekumar G Pillai; Craig P Hersh Journal: BMC Med Genomics Date: 2015-01-13 Impact factor: 3.063
Authors: Christine M Freeman; Fernando J Martinez; Meilan K Han; George R Washko; Alexandra L McCubbrey; Stephen W Chensue; Douglas A Arenberg; Catherine A Meldrum; Lisa McCloskey; Jeffrey L Curtis Journal: Respir Res Date: 2013-02-01