Enhanced cytotoxic function of natural killer and natural killer T-like cells associated with decreased CD94 (Kp43) in the chronic obstructive pulmonary disease airway.
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.
Lung Research Laboratory, Hanson Institute, Adelaide, SA, Australia. greg.hodge@health.sa.gov.au
Greg
G
Hodge
Violet
V
Mukaro
Mark
M
Holmes
Paul N
PN
Reynolds
Sandra
S
Hodge
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D018893:Bronchoalveolar Lavage; D016022:Case-Control Studies; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism / Q000473:pathology*; D037181:Lectins, C-Type / Q000378:metabolism; D008875:Middle Aged; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000378:metabolism*; D055611:Natural Killer T-Cells / Q000378:metabolism / Q000473:pathology*; D054353:Perforin / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000473:pathology*; D012137:Respiratory System / Q000378:metabolism* / Q000473:pathology*; D012907:Smoking / Q000378:metabolism; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D053804:Granzymes; D037181:Lectins, C-Type; D051920:NK Cell Lectin-Like Receptor Subfamily D; D054353:Perforin; D000099192:CD69 Antigens