scholarly journals P2‐22: Imaging changes and immune‐checkpoint expression on T cells in bronchoalveolar lavage fluid from patients with pulmonary sarcoidosis

Respirology ◽  
2021 ◽  
Vol 26 (S3) ◽  
pp. 122-122
Keyword(s):  
T Cells ◽  
Bronchoalveolar Lavage ◽  
Immune Checkpoint ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Pulmonary Sarcoidosis

scholarly journals Imaging Changes and Immune-Checkpoint Expression on T Cells in Bronchoalveolar Lavage Fluid from Patients with Pulmonary Sarcoidosis

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1231
Author(s):  
Yasuaki Kotetsu ◽  
Toyoshi Yanagihara ◽  
Kunihiro Suzuki ◽  
Hiroyuki Ando ◽  
Daisuke Eto ◽  
...  
Keyword(s):  
T Cells ◽  
Bronchoalveolar Lavage ◽  
Immune Checkpoint ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Pulmonary Sarcoidosis ◽  
Immune Checkpoint Molecules ◽  
Ct Findings ◽  
Programmed Cell Death 1 ◽  
Spontaneous Improvement

Sarcoidosis is a systemic, granulomatous disease caused by unknown immunological abnormalities. The organs most vulnerable to sarcoidosis are the lungs. Patients often resolve spontaneously, but the lungs can also be severely affected. Although details regarding prognostic factors in sarcoidosis patients with lung involvement remain unclear, several reports have suggested that immune checkpoint molecules are involved in the pathogenesis of sarcoidosis. In this study, we divided sarcoidosis patients into two groups based on chest computed tomography (CT) findings and compared immune checkpoint molecules expressed on T cells in bronchoalveolar lavage fluid (BALF) in the two groups, using flow cytometry. We found elevated programmed cell death 1 (PD-1) or T cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) expression on T cells in BALF in patients with spontaneous improvement in CT findings, compared with those in patients without improvement in CT findings. In conclusion, our study implies that PD-1 or TIM-3 expression on T cells in BALF may be a prognostic factor for pulmonary lesions in sarcoidosis.

scholarly journals Immune-checkpoint profiles for T cells in bronchoalveolar lavage fluid of patients with immune-checkpoint inhibitor-related interstitial lung disease

2020 ◽  
Vol 32 (8) ◽  
pp. 547-557 ◽  
Author(s):  
Kunihiro Suzuki ◽  
Toyoshi Yanagihara ◽  
Koichiro Matsumoto ◽  
Hitoshi Kusaba ◽  
Takuji Yamauchi ◽  
...  
Keyword(s):  
T Cells ◽  
Interstitial Lung Disease ◽  
Bronchoalveolar Lavage ◽  
Lung Disease ◽  
Cd8 T Cells ◽  
Immune Checkpoint ◽  
Bronchoalveolar Lavage Fluid ◽  
Checkpoint Inhibitors ◽  
Fatal Case ◽  
Lavage Fluid

Abstract Immune-checkpoint inhibitors (ICIs) have improved clinical outcomes and are becoming a standard treatment for many cancer types. However, these drugs also induce immune-related adverse events, among which interstitial lung disease (ILD) is potentially fatal. The underlying mechanism of ILD induction by ICIs is largely unknown. With the use of flow cytometry, we determined the expression levels of the immune-checkpoint proteins PD-1, TIM-3, TIGIT, LAG-3 and PD-L1 in T cells of bronchoalveolar lavage fluid (BALF) from patients with ICI-related ILD and compared them with those for patients with sarcoidosis or with ILD related to connective tissue disease or cytotoxic drug use. The proportions of CD8+ T cells positive for both PD-1 and TIM-3 or for TIGIT in BALF were significantly higher for ICI-related ILD patients than for those with other types of ILD. A prominent increase in the proportion of PD-1+PD-L1+ cells among CD8+ T cells was also apparent in BALF of a patient with a fatal case of ICI-related ILD, and the proportion of such cells was positively correlated with the grade of ICI-related ILD. Our data reveal the immune-checkpoint profiles of T cells in ICI-related ILD and may provide mechanistic insight into the development of this adverse event.

scholarly journals Bronchoalveolar Lavage Fluid IFN-γ+Th17 Cells and Regulatory T Cells in Pulmonary Sarcoidosis

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Anders Tøndell ◽  
Torolf Moen ◽  
Magne Børset ◽  
Øyvind Salvesen ◽  
Anne Dorthea Rø ◽  
...  
Keyword(s):  
T Cells ◽  
Bronchoalveolar Lavage ◽  
Th17 Cells ◽  
Bronchoalveolar Lavage Fluid ◽  
Immune Cell ◽  
Lavage Fluid ◽  
Pulmonary Sarcoidosis ◽  
T Cell Subsets ◽  
Diffuse Parenchymal Lung Diseases ◽  
Cell Fractions

In sarcoidosis, increased Th17 cell fractions have been reported in bronchoalveolar lavage fluid, and elevated numbers of Th17 cells producing IFN-γhave been observed in peripheral blood. The balance between Th1, Th17, and FoxP3+CD4+T cell subsets in sarcoidosis remains unclear. Bronchoalveolar lavage fluid cells, from 30 patients with sarcoidosis, 18 patients with other diffuse parenchymal lung diseases, and 15 healthy controls, were investigated with flow cytometry for intracellular expression of FoxP3. In a subset of the patients, expression of the cytokines IL17A and IFN-γwas investigated. The fractions of FoxP3+CD4+T cells and Th17 cells were both lower in sarcoidosis compared to controls (P=0.017andP=0.011, resp.). The proportion of Th17 cells positive for IFN-γwas greater in sarcoidosis than controls (median 72.4% versus 31%,P=0.0005) and increased with radiologic stage (N=23,rho=0.45, andP=0.03). IFN-γ+Th17 cells were highly correlated with Th1 cells (N=23,rho=0.64, andP=0.001), and the ratio of IFN-γ+Th17/FoxP3+CD4+T cells was prominently increased in sarcoidosis. IFN-γ+Th17 cells may represent a pathogenic subset of Th17 cells, yet their expression of IFN-γcould be a consequence of a Th1-polarized cytokine milieu. Our results indicate a possible immune cell imbalance in sarcoidosis.

CD25+ Regulatory T Cells in Bronchoalveolar Lavage Fluid Are Associated with Lung Allograft Rejection

2014 ◽  
Vol 33 (4) ◽  
pp. S300 ◽  
Author(s):  
J.R. Greenland ◽  
C.M. Wong ◽  
R. Ahuja ◽  
M. Gottschall ◽  
N.N. Trivedi ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Bronchoalveolar Lavage ◽  
Allograft Rejection ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid

scholarly journals T-cell receptor–HLA-DRB1 associations suggest specific antigens in pulmonary sarcoidosis

2015 ◽  
Vol 47 (3) ◽  
pp. 898-909 ◽  
Author(s):  
Johan Grunewald ◽  
Ylva Kaiser ◽  
Mahyar Ostadkarampour ◽  
Natalia V. Rivera ◽  
Francesco Vezzi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Bronchoalveolar Lavage ◽  
T Cell Receptor ◽  
Three Dimensional ◽  
Lavage Fluid ◽  
Cell Receptor ◽  
Pulmonary Sarcoidosis ◽  
Receptor Expression ◽  
Contact Points

In pulmonary sarcoidosis, CD4+ T-cells expressing T-cell receptor Vα2.3 accumulate in the lungs of HLA-DRB1*03+ patients. To investigate T-cell receptor-HLA-DRB1*03 interactions underlying recognition of hitherto unknown antigens, we performed detailed analyses of T-cell receptor expression on bronchoalveolar lavage fluid CD4+ T-cells from sarcoidosis patients.Pulmonary sarcoidosis patients (n=43) underwent bronchoscopy with bronchoalveolar lavage. T-cell receptor α and β chains of CD4+ T-cells were analysed by flow cytometry, DNA-sequenced, and three-dimensional molecular models of T-cell receptor-HLA-DRB1*03 complexes generated.Simultaneous expression of Vα2.3 with the Vβ22 chain was identified in the lungs of all HLA-DRB1*03+ patients. Accumulated Vα2.3/Vβ22-expressing T-cells were highly clonal, with identical or near-identical Vα2.3 chain sequences and inter-patient similarities in Vβ22 chain amino acid distribution. Molecular modelling revealed specific T-cell receptor-HLA-DRB1*03-peptide interactions, with a previously identified, sarcoidosis-associated vimentin peptide, (Vim)429–443 DSLPLVDTHSKRTLL, matching both the HLA peptide-binding cleft and distinct T-cell receptor features perfectly.We demonstrate, for the first time, the accumulation of large clonal populations of specific Vα2.3/Vβ22 T-cell receptor-expressing CD4+ T-cells in the lungs of HLA-DRB1*03+ sarcoidosis patients. Several distinct contact points between Vα2.3/Vβ22 receptors and HLA-DRB1*03 molecules suggest presentation of prototypic vimentin-derived peptides.

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