| Autor: |
McKendry, Richard T., Spalluto, C. Mirella, Burke, Hannah, Nicholas, Ben, Cellura, Doriana, Al-Shamkhani, Aymen, Staples, Karl J., Wilkinson, Tom M.A. |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Předmět: |
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| Popis: |
Rationale: COPD patients are susceptible to respiratory viral infections which cause exacerbations. Mechanisms underlying susceptibility are not understood. Effectors of the adaptive immune response; CD8+ T cells which clear viral infections, are present in increased numbers in lungs of COPD patients but fail to protect against infection and may contribute to the immunopathology of the disease. Objectives: CD8+ function and signalling through the Programmed Cell Death (PD-1) exhaustion pathway was investigated as a potential key mechanism of viral exacerbation of the COPD lung. Methods: Tissue from control or COPD patients undergoing lung resection was infected with live influenza virus ex vivo. Viral infection and expression of lung cell markers was analysed using flow cytometry. Measurements and Main Results: The proportion of lung CD8+ T cells expressing PD-1 was greater in COPD(mean=16.2%) than controls(4.4%, p=0.029). Only epithelial cells and macrophages were infected with influenza and there was no difference in the proportion of infected cells between controls and COPD. Infection upregulated T cell PD-1 expression in control and COPD samples. Concurrently, influenza significantly upregulated the marker of cytotoxic degranulation (CD107a) on CD8+ T cells(p=0.03) from controls, but not from COPD patients. Virus-induced expression of the ligand PD-L1 was decreased on COPD macrophages(p=0.04) with a corresponding increase in IFN? release from infected COPD explants compared to controls(p=0.04). Conclusions: This study has established a signal of cytotoxic immune dysfunction and aberrant immune regulation in the COPD lung that may explain both the susceptibility to viral infection and the excessive, inflammation associated with exacerbations. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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