CD8 + ve Cells in the Lungs of Smokers with Chronic Obstructive Pulmonary Disease

Saetta, Marina; Baraldo, Simonetta; Corbino, Laura; Turato, Graziella; Braccioni, Fausto; Rea, Federico; Cavallesco, Giorgio; Tropeano, Giuseppe; Mapp, C. E.; Maestrelli, Piero; Ciaccia, A.; Fabbri, Leonardo

doi:10.1164/ajrccm.160.2.9812020

Cited by 419 publications

(364 citation statements)

References 23 publications

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“…The numbers of macrophages and CD8+ T-cells in the bronchial mucosa and peripheral lung tissue correlate with a decline in lung function, indicating a role for these cells in the pathogenesis of COPD [2][3][4][5][6] . Studies of tissue samples from smokers and COPD patients have shown increased numbers of CD8+ T-cells in comparison to healthy control subjects, yet few studies have described the function of the these cells.…”

Section: Introductionmentioning

confidence: 99%

αEβ7 Expression on CD8+ T-Cells in COPD BAL Fluid and on TGF-β Stimulated T-Cells In Vitro

Glader

Löfdahl

Wachenfeldt

2005

Lung

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The airway inflammation in patients with COPD shows increased numbers of CD8+ T-cells.Hitherto, few studies have shown any functional data indicating a role for these cells in the pathogenesis of COPD. This paper focuses on a subset of CD8+ T-cells present in human lung, the intra epithelial lymphocytes expressing the integrin αEβ7, and their presence in bronchoalveolar lavage fluid from COPD patients. In this study we demonstrate that 64-89% of the CD8+ T-cells in bronchoalveolar lavage fluid from COPD patients are positive for CD103, the alpha-subunit of αEβ7. We also present an in vitro system in which it is possible to differentiate peripheral T-cells into a phenotype resembling the one found in bronchoalveolar lavage fluid, i.e. CD8+ CD103+. In this in vitro system we demonstrate that, in addition to TGF-β 1 , cell-to-cell interaction between the T-cell and an antigen-presenting cell, here represented by the monocyte, is crucial for a rapid, high and sustained expression of CD103. The signal provided by the monocytes, is shown to be mediated through LFA-1 on the T-cell. Furthermore, differentiation of CD8+ T-cells by TGF-β 1 and monocytes results in down regulation of INF-γ, TNF-α and GM-CSF production. IL-8 production is however retained in the αEβ7 expressing cells. We see this work as an initiation on the quest for a functional characterization of one the different types of CD8+ T cells present in COPD. In the longer perspective we hope this can lead to an increased understanding of how these cells can contribute to the disease pathology.

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Section: Introductionmentioning

confidence: 99%

αEβ7 Expression on CD8+ T-Cells in COPD BAL Fluid and on TGF-β Stimulated T-Cells In Vitro

Glader

Löfdahl

Wachenfeldt

2005

Lung

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“…Increased numbers of CD8+ T-cells, alveolar macrophages and neutrophils are characteristic pathological features of the lungs in COPD [3,4]. Eosinophil numbers are increased during exacerbations and possibly also during stable phases in a subset of patients [5].…”

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confidence: 99%

“…Eosinophil numbers are increased during exacerbations and possibly also during stable phases in a subset of patients [5]. These activated inflammatory cells can release various mediators, including leukotriene B 4 and inflammatory cytokines (e.g. Thelper cell (Th) types 1 and 2 cytokines, and tumour necrosis factor (TNF)-a) [6].…”

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confidence: 99%

Interleukin-18 production and pulmonary function in COPD

Imaoka

Hoshino

Takei³

et al. 2008

European Respiratory Journal

122

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Interleukin (IL)-18 production and pulmonary function were evaluated in patients with chronic obstructive pulmonary disease (COPD) in order to determine the role of IL-18 in COPD.Immunohistochemical techniques were used to examine IL-18 production in the lungs of patients with very severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage IV, n516), smokers (n527) and nonsmokers (n523). Serum cytokine levels and pulmonary function were analysed in patients with GOLD stage I-IV COPD (n562), smokers (n534) and nonsmokers (n547).Persistent and severe small airway inflammation was observed in the lungs of ex-smokers with very severe COPD. IL-18 proteins were strongly expressed in alveolar macrophages, CD8+ Tcells, and both the bronchiolar and alveolar epithelia in the lungs of COPD patients. Serum levels of IL-18 in COPD patients and smokers were significantly higher than those in nonsmokers. Moreover, serum levels of IL-18 in patients with GOLD stage III and IV COPD were significantly higher than in smokers and nonsmokers. There was a significant negative correlation between serum IL-18 level and the predicted forced expiratory volume in one second in patients with COPD. In contrast, serum levels of IL-4, IL-13 and interferon-c were not significantly increased in any of the three groups.In conclusion, overproduction of interleukin-18 in the lungs may be involved in the pathogenesis of chronic obstructive pulmonary disease.

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“…Previous studies have shown an increased number of inflammatory cells [8,9] in pulmonary arteries from patients with COPD. Inflammatory cells are a source of cytokines and growth factors that may contribute to the development of structural and functional abnormalities of the vessel wall [23].…”

Section: Discussionmentioning

confidence: 89%

“…By contrast, at variance with primary hypertension, the medial layer of the arteries is normal or only mildly thickened [6]. These structural changes are often associated with functional impairment of the endothelium [7] and with an inflammatory process in the adventitial layer [8,9]. The mechanisms underlying the development of these structural abnormalities in pulmonary arteries are still unknown.…”

mentioning

confidence: 99%

Transforming growth factor- type II receptor in pulmonary arteries of patients with very severe COPD

Beghè¹,

Bazzan²,

Baraldo³

et al. 2006

European Respiratory Journal

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A mild-to-moderate increase in pulmonary arterial pressure is often associated with severe chronic obstructive pulmonary disease (COPD). Transforming growth factor (TGF)-b is a cytokine involved in the maintenance of integrity of vasculature. The aim of the study was to investigate whether the TGF-b pathway might be involved in the development of pulmonary hypertension associated with COPD.Surgical specimens from 14 patients undergoing lung transplantation for very severe COPD (forced expiratory volume in one second 17¡2% of the predicted value) and from seven donors were examined. The expression of TGF-b1 and TGF-b type II receptor (TGF-bRII), cell proliferation index and structural changes in pulmonary arteries were quantified immunohistochemically.In severe COPD patients, increased expression of TGF-bRII was observed in both the tunica media and intima, which was associated with a normal proliferation index in both layers. Conversely, significant thickening of the tunica intima, which was not present in the tunica media, was observed, suggesting that mechanisms other than cell proliferation may be involved in intimal thickening.In conclusion, in the pulmonary arteries of patients with severe chronic obstructive pulmonary disease, there is upregulation of transforming growth factor-b type II receptor expression associated with a normal proliferation index. These findings suggest the activation of an antiproliferative pathway, which might explain the relatively low degree of pulmonary hypertension observed in these subjects.

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CD8 + ve Cells in the Lungs of Smokers with Chronic Obstructive Pulmonary Disease

Cited by 419 publications

References 23 publications

αEβ7 Expression on CD8+ T-Cells in COPD BAL Fluid and on TGF-β Stimulated T-Cells In Vitro

αEβ7 Expression on CD8+ T-Cells in COPD BAL Fluid and on TGF-β Stimulated T-Cells In Vitro

Interleukin-18 production and pulmonary function in COPD

Transforming growth factor- type II receptor in pulmonary arteries of patients with very severe COPD

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