Mucosal-Associated Invariant T Cell Deficiency in Chronic Obstructive Pulmonary Disease

Figures & data

Table 1.  Clinical and laboratory characteristics of 45 COPD patients

	COPD
Males/Females, n	42/3
Age, mean ± SD (years)	69.5 ± 6.9
Clinical variables, mean ± SD
Current smokers/Former smokers/Non-smokers, n (%)	19(42.2)/20(44.4)/6(13.4)
Smoking (pack-years)	36.2 ± 22.8
FVC (L)	3.1 ± 0.9
FVC (%)	85.1 ± 23.9
FEV1 (L)	1.3 ± 0.6
FEV1 (%)	55.2 ± 22.5
FEV1/FVC (%)	44.6 ± 14.1
TLC (L)	6.2 ± 2.2
TLC (%)	114.2 ± 36.6
DLCO	10.7 ± 4.4
DLCO/VA	3.0 ± 0.9
PaO2 (mmHg)	68.2 ± 12.2
PaCO2 (mmHg)	43.6 ± 12.7
MMRC score	3.1 ± 1.4
Acute exacerbation, n (%)	26 (57.8)
Inhaled corticosteroids, n (%)	34 (75.6)
Daily dose of inhaled corticosteroids, μg of equivalent dose of fluticasone	508.8 ± 184.8
Systemic steroids, n (%)	9 (20.0)
Daily dose of systemic corticosteroid, mg of equivalent dose of prednisolone	38.8 ± 3.5
Co-morbid conditions, n (%)
Diabetes mellitus	4 (8.9)
Cardiovascular disease	10 (22.2)
Chronic liver disease	2 (4.4)
Neurologic disease	1 (2.2)
Laboratory variables, mean ± SD
Hemoglobin (g/dL)	13.9 ± 1.6
Leukocytes (cells/μL)	8,974 ± 4,452
Lymphocytes (cells/μL)	1,391 ± 587.7
Neutrophils (cells/μL)	6,664 ± 4,473
Platelets (10^3 cells/μL)	234.8 ± 75.2
CRP (mg/dL)	3.9 ± 7.1
ESR (mm/hour)	29.7 ± 18.2

BMI, body mass index; COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; DL_CO, diffusing capacity of the lung for carbon monoxide; ESR, erythrocyte sedimentation rate; FEV₁, post-bronchodilator forced expiratory volume in 1 second; FVC, forced vital capacity; MMRC, modified Medical Research Council dyspnea scale measurement; N, number; SD, standard deviation; TLC, total lung capacity; VA, alveolar volume.

Figure 1.  Reduced circulating mucosal-associated invariant T (MAIT) cell numbers in the peripheral blood samples of chronic obstructive pulmonary disease (COPD) patients. Freshly isolated peripheral blood mononuclear cells from 57 healthy controls (HCs) and 45 COPD patients were stained with allophycocyanin (APC)-Alexa Fluor 750-conjugated anti-CD3 and fluorescein isothiocyanate-conjugated anti-CD161 monoclonal antibodies and then analyzed by flow cytometry. Percentages of MAIT cells were calculated using a αβ T cell gate. (a) Representative MAIT cell percentages as determined by flow cytometry. (b) MAIT cell percentages among peripheral blood αβ T cells. (c) Absolute MAIT cell numbers (per microliter of blood). Symbols represent individual subjects and horizontal lines indicate median values. (d) MAIT cell subset percentages among peripheral blood αβ T cells. Data are shown as box plots. Each box represents the 25th and 75th percentiles. Lines inside the boxes represent the median. Whiskers represent the 10th and 90th percentiles. *p < 0.05, **p < 0.005.

Table 2.  Regression coefficients for log-transformed percentage of MAIT cells with respect to clinical and laboratory parameters in the 45 COPD patients

	Univariate			Multivariate
Variable	β	SE	p value	β	SE	p value
Age (years)	0.014	0.011	0.209
BMI	0.007	0.023	0.765
Smoking (pack-years)	−0.005	0.004	0.146
FVC (L)	−0.132	0.080	0.110
FVC (%)	−0.003	0.003	0.414
FEV1 (L)	0.062	0.131	0.640
FEV1 (%)	0.004	0.003	0.226
FEV1/FVC (%)	0.014	0.005	0.007	0.013	0.005	0.014
TLC (L)	−0.008	0.037	0.829
TLC (%)	0.001	0.002	0.759
DLCO	−0.012	0.018	0.488
DLCO/VA	0.033	0.085	0.701
PaO2 (mmHg)	0.001	0.011	0.936
PaCO2 (mmHg)	−0.002	0.009	0.861
Hemoglobin count (g/dL)	−0.079	0.052	0.137
Leukocyte count (cells/μL)	0.000	0.000	0.331
Lymphocyte count (cells/μL)	0.000	0.000	0.673
Neutrophil count (cells/μL)	0.000	0.000	0.367
Platelet count (10^3 cells/μL)	0.000	0.001	0.941
CRP level (mg/dL)	−0.023	0.010	0.033	−0.014	0.010	0.196
ESR (mm/hour)	−0.004	0.005	0.475
CD3+ T cell level	0.003	0.005	0.603
CD3+TCRγδ+ cell level	0.002	0.053	0.966

β, regression coefficients; BMI, body mass index; COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; DL_CO, diffusing capacity of the lung for carbon monoxide; ESR, erythrocyte sedimentation rate; FEV₁, post-bronchodilator forced expiratory volume in one second; FVC, forced vital capacity; SE, standard error; TLC, total lung capacity; VA, alveolar volume.

Figure 2.  Reduced circulating mucosal-associated invariant T (MAIT) cell frequency in patients with advanced stage of chronic obstructive pulmonary disease (COPD). Freshly isolated peripheral blood mononuclear cells from 45 COPD patients were stained with allophycocyanin (APC)-Alexa Fluor 750-conjugated anti-CD3 and fluorescein isothiocyanate-conjugated anti-CD161 monoclonal antibodies and then analyzed by flow cytometry. According to the Global initiative for Chronic Obstructive Lung Disease (GOLD) grading system, the severity of COPD can be subclassified into GOLD 1 (mild), GOLD 2 (moderate), GOLD 3 (severe), and GOLD 4 (very severe). Percentages of MAIT cells were calculated using a αβ T cell gate. Symbols represent individual subjects and horizontal lines indicate median values. *p < 0.05.