Specific bronchoalveolar lavage fluid T cells associate with disease in a pair of monozygotic twins discordant for sarcoidosis

ABSTRACT Regulatory CD4+ T cells have been shown to be important in limiting immune responses, but their role in respiratory viral infections has received little attention. Here we observed that following respiratory syncytial virus (RSV) infection, CD4+ Foxp3+ CD25+ natural regulatory T-cell numbers increased in the bronchoalveolar lavage fluid, lung, mediastinal lymph nodes, and spleen. The depletion of CD25+ natural regulatory T cells prior to RSV infection led to enhanced weight loss with delayed recovery that was surprisingly accompanied by increased numbers of activated natural killer cells in the lung and bronchoalveolar lavage fluid on day 8 postinfection. Increased numbers of neutrophils were also detected within the bronchoalveolar lavage fluid and correlated with elevated levels of myeloperoxidase as well as interleukin-6 (IL-6) and gamma interferon (IFN-γ). CD25+ natural regulatory T-cell depletion also led to enhanced numbers of proinflammatory T cells producing IFN-γ and tumor necrosis factor alpha (TNF-α) in the lung. Despite these increases in inflammatory responses and disease severity, the viral load was unaltered. This work highlights a critical role for natural regulatory T cells in regulating the adaptive and innate immune responses during the later stages of lung viral infections.

Download Full-text

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

Biomedicines ◽

10.3390/biomedicines9091231 ◽

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.

Download Full-text