Blunted γδ T-lymphocyte response in chronic obstructive pulmonary disease

Pons, Jaume; Sauleda, Jaume; Ferrer, J.M. Escribano; Barceló, Bernardino; Fuster, Antònia; Regueiro, Verónica; Juliá, M. R.; Agustí, Àlvar

doi:10.1183/09031936.05.00069304

Cited by 44 publications

(37 citation statements)

References 28 publications

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“…The present results are in agreement with study of LEE et al [18], which demonstrated decreased CD4+CD25+ Treg cell number in lung tissue from emphysema patients, which in turn correlated with FOXP3 mRNA expression. This pattern of FOXP3-positive Treg cells response in small airways of COPD patients is in fact very similar to that of cd T-lymphocytes obtained from bronchoalveolar lavage fluid, which is another subpopulation of T-lymphocytes involved in tissue repair [26]. Furthermore, as illustrated in an animal model, Treg lymphocytes knockout mice (characteristics of this T-cell subset are strikingly similar between mouse and man) exhibit markedly increased inflammatory responses [27].…”

Section: Discussionmentioning

confidence: 81%

Decreased FOXP3 expression in small airways of smokers with COPD

Isajevs

Taivāns²,

Strazda³

et al. 2008

Eur Respir J

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CD4+CD25+ FOXP3-positive T-regulatory cells have an important role in controlling immune and inflammatory reactions. The present authors hypothesise that these cells may be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of the present study was to characterise the expression of FOXP3 in large and small airways of nonsmokers, smokers with normal lung function and COPD patients.A total of 19 nonsmokers, 20 smokers with normal lung function and 20 smokers with moderate COPD, undergoing lung resection for a solitary peripheral nonsmall cell carcinoma, were enrolled in the study. Immunohistochemical methods were used to evaluate FOXP3 expression in large and small airways.Smokers with normal lung function and COPD patients had increased numbers of FOXP3-positive cells in large airways compared with nonsmokers. A positive correlation was observed between FOXP3 expression in large airways and smoked pack-yrs. In small airways, COPD patients had decreased numbers of FOXP3-positive cells, compared with asymptomatic smokers and nonsmokers, that negatively correlated with airflow obstruction.To conclude, chronic obstructive pulmonary disease is characterised by upregulation of FOXP3-positive cells in large airways but a downregulation in small airways that correlated with airflow limitation. The results of the present study contribute to a better understanding of the pathogenesis of chronic obstructive pulmonary disease.

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Section: Discussionmentioning

confidence: 81%

Decreased FOXP3 expression in small airways of smokers with COPD

Isajevs

Taivāns²,

Strazda³

et al. 2008

Eur Respir J

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“…They pointed out a need for follow-up of these children to assess the possible health implications of their findings. Therefore, since the distribution of TCR can vary according to age and genetic factors, the correlation between PCB and TCR found in our exposed workers seems to indicate a stimulation of the specific expression of TCR a-~involved in lymphocyte antigen recognition (23). On the contrary, the results of the study seem to exclude a direct effect of smoke and alcohol on TCR a-~and y-8 cells , in contrast with findings of some authors reporting an effect of smoke on TCR y-8 cells in humans and in mice (23,24).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, since the distribution of TCR can vary according to age and genetic factors, the correlation between PCB and TCR found in our exposed workers seems to indicate a stimulation of the specific expression of TCR a-~involved in lymphocyte antigen recognition (23). On the contrary, the results of the study seem to exclude a direct effect of smoke and alcohol on TCR a-~and y-8 cells , in contrast with findings of some authors reporting an effect of smoke on TCR y-8 cells in humans and in mice (23,24). More intriguing and original, in PCB exposed subjects, is the relative % reduction of TCR y-8 T cells, in human particularly present in epithelia, both in the peripheral blood on the number of cigarettes smoked per day confirms the immunomodulating action of tobacco smoking that has already been reported by other authors, who found a greater and significant increase of Treg in bronchial alveolar lavage (BAL) of healthy smokers as compared to non-smokers/ex-smokers/smokers with chronic obstructive pulmonary disease (COPD) (9,10,30).…”

Section: Discussionmentioning

confidence: 99%

Immune Effects and Polychlorinated Biphenyls, Smoking and Alcohol

D’Errico

Tullio

Gioacchino

et al. 2012

Int J Immunopathol Pharmacol

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Polychlorinated biphenyls (PCB) have been shown to exert some immune effects. Here we analysed their effects also on immune parameters not previously studied such as TCR a-p, TCR "(-0 and regulatory T cells (Treg), taking into account the specific and cumulative interference of smoking and alcohol. The study subjects consisted of26 male workers in a steelworks factory, employed in the electrical maintenance sector, with previous exposure to a mixture of PCB (exposed subjects), and 30 male workers with no occupational exposure to PCB (controls). All subjects were given a questionnaire and peripheral venous blood samples were taken to determine serum PCB (33 congeners), total cholesterol and triglycerides, leukocytes, total lymphocytes and the T lymphocyte subpopulations (TCR a-p, TCR"(-o, CD4+ and Treg lymphocytes). PCB, even though at a very low concentration, were significantly higher in exposed subjects than controls, and were significantly correlated with age. Monocytes% and CD4+ were significantly reduced in the exposed subjects as compared to the controls. The serum concentration of PCB positively correlated with TCR a-p, and negatively with TCR"(-o. Treg lymphocytes showed a positive dependence on tobacco smoking, while the monocytes% and CD4+ showed a negative and positive dependence, respectively, on alcohol intake. Our results seem to show some effects of slight exposure to PCB in particular reducing the relative concentration of TCR"(-o. This effect can favour indirectly the increase in Treg induced by smoking, the anti-inflammatory or proinflammatory/fibrogenetic/angiogenetic effect of which, exerted by produced cytokines, particularly TGF-13, deserves further clarification.Polychlorinated biphenyl (PCB) family includes 209 different synthetic organic biphenyl compounds, with variable substitutions of the hydrogen atoms by chlorine atoms. Due to their remarkable insulating capacity and resistance to fire and oxidants, as well as their marked chemical stability, these compounds were widely used in industrialized nations between 1940 and 1980. Their main applications were as

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“…Subset analysis has shown a slight increase in CD4+ cells expressing interferon (IFN)-c and a decrease in cells expressing IL-4, indicating Th1 predominance in the peripheral circulation, with no changes in CD8+ cell subsets [55]. Circulating cd T-cells are increased in normal smokers but not in COPD patients [56].…”

Section: Lymphocytesmentioning

confidence: 99%

Systemic manifestations and comorbidities of COPD

Barnes¹,

Celli²

2009

Eur Respir J

1,476

1,113

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Increasing evidence indicates that chronic obstructive pulmonary disease (COPD) is a complex disease involving more than airflow obstruction. Airflow obstruction has profound effects on cardiac function and gas exchange with systemic consequences. In addition, as COPD results from inflammation and/or alterations in repair mechanisms, the ''spill-over'' of inflammatory mediators into the circulation may result in important systemic manifestations of the disease, such as skeletal muscle wasting and cachexia. Systemic inflammation may also initiate or worsen comorbid diseases, such as ischaemic heart disease, heart failure, osteoporosis, normocytic anaemia, lung cancer, depression and diabetes. Comorbid diseases potentiate the morbidity of COPD, leading to increased hospitalisations, mortality and healthcare costs. Comorbidities complicate the management of COPD and need to be evaluated carefully. Current therapies for comorbid diseases, such as statins and peroxisome proliferator-activated receptor-agonists, may provide unexpected benefits for COPD patients. Treatment of COPD inflammation may concomitantly treat systemic inflammation and associated comorbidities. However, new broad-spectrum anti-inflammatory treatments, such as phosphodiesterase 4 inhibitors, have significant side-effects so it may be necessary to develop inhaled drugs in the future. Another approach is the reversal of corticosteroid resistance, for example with effective antioxidants. More research is needed on COPD comorbidities and their treatment.

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Blunted γδ T-lymphocyte response in chronic obstructive pulmonary disease

Cited by 44 publications

References 28 publications

Decreased FOXP3 expression in small airways of smokers with COPD

Decreased FOXP3 expression in small airways of smokers with COPD

Immune Effects and Polychlorinated Biphenyls, Smoking and Alcohol

Systemic manifestations and comorbidities of COPD

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