New aid for diagnosing chronic beryllium disease (CBD): laser ion mass analysis (LIMA).

Williams, W. T.; Kelland, D.

doi:10.1136/jcp.39.8.900

Cited by 21 publications

(12 citation statements)

References 3 publications

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“…The majority of T-cell clones expressing this shared motif persist over time, suggesting persistent antigen stimulation [25]. These findings are consistent with studies using laser ion mass analysis, which have identified beryllium in the lungs of patients years after removal from the source of exposure [18,19].…”

Section: Beryllium-specific Cd4 C T Cells In Cbdsupporting

confidence: 85%

“…The histopathology of CBD is identical to that seen in sarcoidosis, a more common granulomatous lung disease of unknown etiology [16,17]. Owing to the persistent presence of beryllium in the lung years after exposure cessation [18,19], the natural history of disease is characterized by a gradual decline in lung function. Historically, one-third of untreated patients progress to end-stage respiratory insufficiency [20].…”

Section: Introductionmentioning

confidence: 97%

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Genetic susceptibility and immune-mediated destruction in beryllium-induced disease

Fontenot

Maier

2005

Trends in Immunology

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Section: Beryllium-specific Cd4 C T Cells In Cbdsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 97%

Genetic susceptibility and immune-mediated destruction in beryllium-induced disease

Fontenot

Maier

2005

Trends in Immunology

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“…Studies (61)(62)(63) have identified beryllium in the lungs of CBD patients years after beryllium exposure cessation. Consistent with the persistence of beryllium in the lung, we have also identified persistent oligoclonal T cell populations in the lungs of CBD patients at every time point analyzed over a 5-year period (14).…”

Section: Discussionmentioning

confidence: 99%

Recombinant HLA-DP2 Binds Beryllium and Tolerizes Beryllium-Specific Pathogenic CD4+ T Cells

Fontenot

Keizer

McCleskey

et al. 2006

The Journal of Immunology

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Chronic beryllium disease is a lung disorder caused by beryllium exposure in the workplace and is characterized by granulomatous inflammation and the accumulation of beryllium-specific, HLA-DP2-restricted CD4+ T lymphocytes in the lung that proliferate and secrete Th1-type cytokines. To characterize the interaction among HLA-DP2, beryllium, and CD4+ T cells, we constructed rHLA-DP2 and rHLA-DP4 molecules consisting of the α-1 and β-1 domains of the HLA-DP molecules genetically linked into single polypeptide chains. Peptide binding to rHLA-DP2 and rHLA-DP4 was consistent with previously published peptide-binding motifs for these MHC class II molecules, with peptide binding dominated by aromatic residues in the P1 pocket. 9Be nuclear magnetic resonance spectroscopy showed that beryllium binds to the HLA-DP2-derived molecule, with no binding to the HLA-DP4 molecule that differs from DP2 by four amino acid residues. Using beryllium-specific CD4+ T cell lines derived from the lungs of chronic beryllium disease patients, beryllium presentation to those cells was independent of Ag processing because fixed APCs were capable of presenting BeSO4 and inducing T cell proliferation. Exposure of beryllium-specific CD4+ T cells to BeSO4-pulsed, plate-bound rHLA-DP2 molecules induced IFN-γ secretion. In addition, pretreatment of beryllium-specific CD4+ T cells with BeSO4-pulsed, plate-bound HLA-DP2 blocked proliferation and IL-2 secretion upon re-exposure to beryllium presented by APCs. Thus, the rHLA-DP2 molecules described herein provide a template for engineering variants that retain the ability to tolerize pathogenic CD4+ T cells, but do so in the absence of the beryllium Ag.

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“…Taken together, these finding demonstrate that PD-1 is up-regulated on T cells that are responsive to persistent Ag to down-regulate the function of T cells which are aberrantly responding to autoantigens or to shut off a chronic inflammatory response to a pathogen. Due to the persistence of beryllium in the lung long after the cessation of exposure (22)(23)(24), aberrant regulation of the PD-1 pathway may play an important role in the development of CBD.…”

Section: Up-regulation Of Programmed Death-1 Expression Onmentioning

confidence: 99%

Up-Regulation of Programmed Death-1 Expression on Beryllium-Specific CD4+ T Cells in Chronic Beryllium Disease

Palmer¹,

Mack²,

Martin³

et al. 2008

The Journal of Immunology

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Chronic beryllium disease (CBD) is caused by workplace exposure to beryllium and is characterized by the accumulation of memory CD4+ T cells in the lung. These cells respond vigorously to beryllium salts in culture by producing proinflammatory Th1-type cytokines. The presence of these inflammatory cytokines leads to the recruitment of alveolar macrophages, alveolitis, and subsequent granuloma development. It has been shown that chronic exposure to conventional Ags leads to up-regulation in the expression of negative regulators of T cells such as programmed death-1 (PD-1). Due to the persistence of beryllium in the lung after the cessation of exposure, aberrant regulation of the PD-1 pathway may play an important role in CBD development. In the present study, PD-1 expression was measured on blood and bronchoalveolar lavage (BAL) CD4+ T cells from beryllium-sensitized and CBD subjects. PD-1 expression was significantly higher on BAL CD4+ T cells compared with those cells in blood, with the highest expression on the beryllium-specific T cell subset. In addition, the expression of PD-1 on BAL CD4+ T cells directly correlated with the severity of the T cell alveolitis. Increased expression of the PD-1 ligands, PD-L1 and PD-L2, on BAL CD14+ cells compared with blood was also seen. The addition of anti-PD-1 ligand mAbs augmented beryllium-induced CD4+ T cell proliferation, and an inverse correlation was seen between PD-1 expression on beryllium-specific CD4+ T cells and beryllium-induced proliferation. Thus, the PD-1 pathway is active in beryllium-induced disease and plays a key role in controlling beryllium-induced T cell proliferation.

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New aid for diagnosing chronic beryllium disease (CBD): laser ion mass analysis (LIMA).

Cited by 21 publications

References 3 publications

Genetic susceptibility and immune-mediated destruction in beryllium-induced disease

Genetic susceptibility and immune-mediated destruction in beryllium-induced disease

Recombinant HLA-DP2 Binds Beryllium and Tolerizes Beryllium-Specific Pathogenic CD4+ T Cells

Up-Regulation of Programmed Death-1 Expression on Beryllium-Specific CD4+ T Cells in Chronic Beryllium Disease

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