Impaired function of regulatory T-cells in patients with chronic obstructive pulmonary disease (COPD) (original) (raw)
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American journal of respiratory and critical care medicine, 2014
Previous studies from our laboratory have shown that peripheral blood mononuclear cells (PBMCs) from patients with chronic obstructive pulmonary disease (COPD) prone to exacerbations with nontypeable Haemophilus influenzae have impaired responses to lipoprotein P6. We hypothesized that an underlying immunosuppressive network could be responsible for the defective antibacterial immunity observed in these patients. We evaluated T regulatory cells (Tregs), myeloid-derived suppressor cells (MDSC), and exhausted T effector cells (programmed death 1 [PD-1](+)) in patients with COPD, because these cells are known to play a pivotal role in suppressing immune responses. We performed an in-depth characterization of Tregs, T effector cells, and MDSC in COPD and correlated their levels and function with disease severity. Treg, effector T cell, and MDSC frequency from patients with COPD and healthy subjects' PBMCs were analyzed by flow cytometry. Treg immunosuppressive capacity was measured ...
Advances in Respiratory Medicine
Introduction: Many theories have been proposed to explain pathogenesis of COPD; however, remains unclear why the majority of smokers (~80%) do not develop COPD, or only develop a mild disease. To explore if COPD has an autoimmune component, the role of T regulatory lymphocytes (Tregs) in the lung tissue of COPD patients is of crucial importance. Material and methods: Bronchial tissue biopsy samples were prospectively collected from 64 patients (39 COPD and 25 controls-15 smokers and 10 non-smokers). The patients with COPD were subdivided into mild/moderate (GOLD stage I−II) and severe/very severe (GOLD stage III−IV) groups. Digital image analysis was performed to estimate densities of CD4+ CD25+ cell infiltrates in double immunohistochemistry slides of the biopsy samples. Blood samples were collected from 42 patients (23 COPD and 19 controls) and tested for CD3+ CD4+ CD25+ bright lymphocytes by flow cytometry. Results: The number of intraepithelial CD4+ CD25+ lymphocytes mm-2 epithelium was significantly lower in the severe/very severe COPD (GOLD III-IV) group as well as in the control non-smokers (NS) group (p < 0,0001). Likewise, the absolute number of Treg (CD3+ CD4+ CD25+ bright) cells in the peripheral blood samples was significantly different between the four groups (p = 0.032). The lowest quantity of Treg cells was detected in the severe/very severe COPD and healthy non-smokers groups. Conclusion: Our findings suggest that severe COPD is associated with lower levels of Tregs in the blood and bronchial mucosa, while higher Tregs levels in the smokers without COPD indicate potential protective effect of Tregs against developing COPD.
Airway regulatory T cells are decreased in COPD with a rapid decline in lung function
Respiratory Research, 2020
Background Differences in the expression of regulatory T cells (Tregs) have been suggested to explain why some smokers develop COPD and some do not. Upregulation of Tregs in response to smoking would restrain airway inflammation and thus the development of COPD; while the absense of such upregulation would over time lead to chronic inflammation and COPD. We hypothesized that—among COPD patients—the same mechanism would affect rate of decline in lung function; specifically, that a decreased expression of Tregs would be associated with a more rapid decline in FEV1. Methods Bronchoscopy with BAL was performed in 52 subjects recruited from the longitudinal OLIN COPD study; 12 with COPD and a rapid decline in lung function (loss of FEV1 ≥ 60 ml/year), 10 with COPD and a non-rapid decline in lung function (loss of FEV1 ≤ 30 ml/year), 15 current and ex-smokers and 15 non-smokers with normal lung function. BAL lymphocyte subsets were determined using flow cytometry. Results The proportions ...
Phenotypic Profiling of Immune Cells and Their Mediators in Chronic Obstructive Pulmonary Disease
Biomedicines
Background: Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder and has been proposed to have an imbalance between pro-inflammatory and anti-inflammatory factors. Methods: This study was conducted on 41 participants {18 COPD patients (smokers, COPD S (n = 9); reformed smokers, COPD RS (n = 9)) and 23 controls (non-smokers, CNS (n = 14); smokers, CS (n = 9))}. Flow cytometry was used to identify circulatory immune cells and correlated with serum cytokines. Results: On comparison, significantly lower frequency of CD3+ T cells were observed in COPD S as compared to CNS (p < 0.01) and CS (p < 0.01); CD4+ T cells were lower in COPD S (p < 0.05), COPD RS (p < 0.05) and CNS (p < 0.01) as compared to CS. CD8+ T cells were elevated in COPD S as compared to CS (p < 0.05). Lower frequency of cDCs were observed in COPD S as compared to CS (p < 0.05) and COPD RS as compared to CNS (p < 0.01) and CS (p < 0.01). Lower frequency of pDCs were observed ...
Clinical & Experimental Immunology, 2007
The role of T cells in the pathophysiology of chronic obstructive pulmonary disease (COPD) is not yet certain, although varying reports have shown increases in T helper 1 (Th1) and/or Th2 cytokines in peripheral blood and bronchoalveolar lavage (BAL). No studies have examined cytokine production by intraepithelial T cells obtained by bronchial brushing (BB). Intracellular cytokine analysis of T cell subsets from peripheral blood, BAL and BB from smoker and ex-smoker COPD patients, COPD patients receiving inhaled corticosteroids and smoker and non-smoker control subjects was studied using multi-parameter flow cytometry. CD4 : CD8 inversion was noted in the peripheral blood of smoker and ex-smoker COPD groups, in BAL and BB from smoker controls and BAL of COPD smokers. There was an increase in intracellular CD8 + T cell Th1 proinflammatory cytokines in some COPD groups in the peripheral blood and in CD8 + T cell tumour necrosis factor (TNF)-a in some COPD groups and smoker controls in BAL and BB. There was an increase in proinflammatory cytokines in COPD smokers compared with ex-smokers and a decrease in COPD smokers receiving inhaled corticosteroids in the airways. There was a negative correlation between forced expiratory volume in 1 s (FEV1) and the percentage of BAL and intraepithelial CD8 + T cells producing TNF-a. COPD patients exhibit systemic inflammation as evidenced by increased intracellular Th1 proinflammatory cytokines in blood, BAL and intraepithelial CD8 + T cells, whereas smoker controls showed localized Th1 response in the lung only. Systemic therapeutic targeting of TNF-a production by CD8 + T cells may improve morbidity in COPD patients while targeting of TNF-a in the lung may prevent smokers progressing to COPD.
Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG / World Association of Sarcoidosis and Other Granulomatous Disorders, 2003
The presence of a heterogeneous infiltrate of macrophages, neutrophils and CD8+ Tc1 cells is a characteristic feature in the lung of patients with chronic obstructive pulmonary disease (COPD). This paper points out the contribution of different inflammatory cells and mediators to the pathogenesis and natural history of COPD. We will comment on data suggesting that CD8 cytotoxic T cells with an activated Tc1 phenotype migrate from the secondary lymphoid tissue to pulmonary tissue damaged by smoke or infective agents. On the basis of the knowledge of the pathophysiology of immunologic events, drugs that can potentially block the inflammation leading to the disability of COPD are being investigated. Long-term study in a large number of patients with COPD will be needed to verify the impact of a number of anti-inflammatory compounds in this increasingly common disease.
Local and Systemic Inflammation in Patients with Chronic Obstructive Pulmonary Disease
American Journal of Respiratory and Critical Care Medicine, 2002
fluid was demonstrated in patients with COPD compared significant chronic inflammation in the pulmonary compartment with control subjects , reflecting neutrophilia in the as well as in the circulation. This study aimed to elucidate the relacentral airways . The extent of neutrophilia correlated tionship between local and systemic inflammation in smoking-inwith the degree of airflow limitation (12, 14, 15). Analysis of duced COPD by assessing levels of soluble (s) tumor necrosis factor induced sputum revealed that levels of interleukin-8 (IL-8) (TNF) receptors, TNF-␣, and interleukin-8 (IL-8) in induced sputum and tumor necrosis factor-␣ (TNF-␣), which are generally and in plasma. Sputum induction was performed in 18 subjects with considered to be important mediators in neutrophil recruit-COPD (FEV 1 56% predicted) and 17 healthy smokers (FEV 1 99% ment, are elevated in patients with COPD (14, 16, 17). In predicted). Patients with COPD showed significantly higher peraddition, elevated levels of neutrophil granule proteins were centages of neutrophils and levels of sTNF-R55 and IL-8 in sputum demonstrated in induced sputum and bronchoalveolar lavage as compared with control subjects, whereas sputum sTNF-R75 levels fluid from patients with severe COPD and smoking subjects tended to be higher in COPD. Sputum TNF-␣ levels were similar in with subclinical emphysema, respectively, indicating activaboth groups. When comparing sTNF receptors in sputum and tion of recruited neutrophils (18, 19). plasma, no direct correlations were found despite elevation of circu-TNF-␣ is a potent proinflammatory cytokine known to lating sTNF-R75 levels in patients with COPD. In addition, sputum exert its activities by interaction with two structurally related, sTNF receptors were inversely related to the FEV 1 in patients with but functionally distinct, transmembrane receptors, referred COPD, whereas circulating sTNF receptors were not, suggesting to as TNF-R55 and TNF-R75 in accordance with their molecdifferent regulation of inflammation in the pulmonary and systemic ular weight (reviewed in Reference 20). Although the two compartment. When subjects were divided according to their curreceptors are independently coexpressed on the surface of rent smoking status, levels of sTNF-R55, sTNF-R75, and IL-8 in sputum were significantly elevated in ex-smoking versus currently most cell types, several studies have shown that TNF-R55 is smoking patients with COPD, suggesting ongoing inflammation mainly expressed on cells of epithelial origin, whereas TNFin airways and circulation of patients with COPD after smoking R75 is primarily found on the cell surface of cells of myeloid cessation. origin (21, 22). A variety of inflammatory stimuli, including endogenous TNF-␣ formation (23), is known to induce pro-Keywords: chronic obstructive pulmonary disease; pulmonary inflamteolytic shedding of the extracellular cytokine-binding domation; systemic inflammation; smoking cessation; tumor necrosis fac-