Sputum T lymphocytes in asthma, COPD and healthy subjects have the phenotype of activated intraepithelial T cells (CD69+ CD103+)

Leckie, Maggie J.; Jenkins, Gavin R.; Khan, Jamey; Smith, Sunny; Walker, Christoph; Barnes, Peter J.; Hansel, Trevor T.

doi:10.1136/thorax.58.1.23

Cited by 61 publications

(65 citation statements)

References 41 publications

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“…2B) also appear to be an unprecedented finding and a possible result of the power afforded by study of comparatively greater subject numbers. Moreover, this particular observation is also consistent with previous findings of increased activations of in situ T cells within COPD lungs (2,3,7,9). Proportions of circulating CD4 T cells were also seen here to decrease among those more severe COPD (Fig.…”

Section: Discussionsupporting

confidence: 92%

“…A growing body of evidence suggests that adaptive immune responses play an important role in the pathogenesis and progression of COPD, as evidenced by correlations of lung histological and morphometric measurements with the characteristics of intrapulmonary lymphocyte infiltrations (2)(3)(4)(5)(6)(7)(8)(9)(10). Moreover, activated T cells can cause a variety of the tissue injuries that typify COPD by direct cytopathic effects, elaboration of diverse proinflammatory and deleterious mediators, and/or recruitment and activation of other immune and parenchymal effector cells (11,12).…”

Section: Hronic Obstructive Pulmonary Disease (Copd)mentioning

confidence: 99%

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Peripheral T Cell Functions Correlate with the Severity of Chronic Obstructive Pulmonary Disease

Zhu

Gadgil

Givelber

et al. 2009

The Journal of Immunology

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Adaptive immune processes have been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). We hypothesized that peripheral T cell abnormalities may be present in afflicted patients. We tested this hypothesis by characterizing circulating T cells in COPD patients and correlated these findings with disease severity, smoking status, and use of inhaled glucocorticosteroids (ICS). Compared with normal controls, a lesser proportion of peripheral CD4 T cells from COPD subjects produced IL-10, whereas the CD8 T cells from these patients were more often activated and more frequently produced both IFN-γ and IL-4. COPD severity was significantly and inversely associated with the proportion of circulating CD4 T cells and directly correlated with CD4 production of IL-2, as well as frequency of CD8 T cell activation and CD8 IFN-γ production. Adjustments for current smoking status and ICS use by linear regression showed independent, and generally inhibitory, effects of these clinical variables on the abnormal T cell functions of these patients. We conclude that circulating T cells from COPD patients are abnormally activated and elaborate proinflammatory mediators with admixed features of Th1 and Th2 responses. Furthermore, many of these effector processes are significantly correlated with disease severity. These findings further implicate adaptive immune processes in COPD progression and indicate that facile assays of peripheral lymphocytes may provide useful insights into disease mechanisms. Current smoking and ICS use had independent effects on T cell functions among the COPD subjects, illustrating the importance of controlling for clinical parameters as covariates in immunological studies of patients afflicted with this disease.

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Section: Discussionsupporting

confidence: 92%

Section: Hronic Obstructive Pulmonary Disease (Copd)mentioning

confidence: 99%

Peripheral T Cell Functions Correlate with the Severity of Chronic Obstructive Pulmonary Disease

Zhu

Gadgil

Givelber

et al. 2009

The Journal of Immunology

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“…As shown in this study BAL CD8+ T-cells from COPD patients do to a large extent express CD103 indicating a need to gain better understanding of these cells in order to understand their potential role in the pathogenesis of COPD. Also for cells in sputum of COPD patients 25-60% of CD8+ T-cells express CD103 [20] . The number of T-cells to be extracted from BAL, in the intention to be used in functional assays, is still very limited.…”

Section: Discussionmentioning

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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“…However, there is little detailed information available regarding FCM gating for leukocyte populations in IS, although strategies for bronchoalveolar lavage (BAL) have been published (3,4). To date, most reports using FCM to analyze IS have focussed on one particular cell subset, such as macrophages (5,6), neutrophils (7), or lymphocytes (8)(9)(10)(11). This may be due in part to the specific difficulties associated with the FCM analysis of IS, including contamination with nonviable cells, or the use of DTT (dithiothreitol) for mucus dispersal, which affects FCM detection of certain cell markers (12).…”

mentioning

confidence: 99%

Identifying leukocyte populations in fresh and cryopreserved sputum using flow cytometry

Brooks

Dalen

Hermans

et al. 2013

Cytometry Part B Clinical

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Background: Airway inflammation is commonly assessed by sputum induction followed by a differential cell count (DCC) using light microscopy. This method is prone to intercounter variability and poor reproducibility. We aimed to develop a more objective method using flow cytometry (FCM).Methods: Fifty-six sputum inductions were conducted in 41 adults (23 asthmatics). Sputum was processed, a cytospin prepared for DCC, and the remainder immunolabeled for FCM using CD45, CD14, and CD16-specific antibodies to distinguish major leukocyte populations. Aliquots of 15 samples were frozen at 280 C to assess the effects of cryostorage. DCC and FCM were compared, and viability of individual cell populations was determined by FCM.Results: FCM and DCC, and fresh and frozen samples, were significantly correlated, R 5 0.54-0.87; all P < 0.0001, and R 5 0.57 to 1; P < 0.005, respectively. There was a significant neutrophil loss after cryostorage (from median 30.5-17.4% of total leukocytes; P < 0.0001). Cell viability was higher for lymphocytes compared to granulocytes or macrophages (P < 0.001). With the exception of the expected higher levels of eosinophils (P < 0.005), no significant difference in cell differentials or viability was observed between asthmatics and nonasthmatics using either DCC or FCM.Conclusions: FCM is a suitable means of assessing leukocyte populations in induced sputum. Sample storage at 280 C prior to FCM is feasible, but may be detrimental to neutrophils, although good correlations were still observed between fresh and frozen samples. Large differences in viability were found between individual cell populations suggesting that viability dye use may be necessary. V C 2013 International Clinical Cytometry Society

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Sputum T lymphocytes in asthma, COPD and healthy subjects have the phenotype of activated intraepithelial T cells (CD69+ CD103+)

Cited by 61 publications

References 41 publications

Peripheral T Cell Functions Correlate with the Severity of Chronic Obstructive Pulmonary Disease

Peripheral T Cell Functions Correlate with the Severity of Chronic Obstructive Pulmonary Disease

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

Identifying leukocyte populations in fresh and cryopreserved sputum using flow cytometry

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