Modulation of PD-1 and PD-L1 expression in response to acute viral infection of human lung tissue

R. McKendry, K. Staples, C. M. Spalluto, T. Wilkinson (Southampton, United Kingdom)

Source: International Congress 2014 – Cell biology 2014
Session: Cell biology 2014
Session type: Thematic Poster Session
Number: 3855
Disease area: Airway diseases, Respiratory infections

Congress or journal article abstract

Abstract

Introduction and Objectives: Acute viral infections are common in healthy individuals without long-term health implications, but these infections can have more serious outcomes for infants, the elderly and immunocompromised individuals. Patients with chronic respiratory conditions, such as COPD, are at greater risk from severe adverse effects of acute respiratory infection. Investigation of how pulmonary immune cells of healthy and COPD patients differ in their responses to viral infection may elucidate defective mechanisms of host defense and allow for intervention to aid disease resolution.Methods: Human lung tissue from control or COPD patients undergoing lung resection surgery was infected with H3N2 strain X31 Influenza A virus (3V Biosciences, CA) or UV-irradiated X31 virus. Tissue was digested using collagenase to generate a single-cell suspension and was labelled with fluorescent antibodies for FACS analysis. The expression of the activation and exhaustion marker PD-1 was analysed on T cells, with the ligand PD-L1 measured on epithelial cells and macrophagess.Results: Proportion of CD4 T cells (mean=3.9%) and CD8 T cells (mean=10.9%) expressing PD-1 is greater in COPD individuals at baseline levels compared to controls (CD4 mean=1.2%, CD8 mean=2.4%). This baseline difference impacts upon PD-1 upregulation in response to X31 infection. Macrophages upregulate PD-L1 in response to infection in both COPD (1.2% to 6.6%, p=0.03) and control (1.3% to 16.6%, p=0.03) samples.Conclusion: Macrophages may play a role in controlling T cell responses to acute viral infection. This effect may be lost with high levels of PD-1 expression in COPD patients independently of X31 infection.


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Citations should be made in the following way:
R. McKendry, K. Staples, C. M. Spalluto, T. Wilkinson (Southampton, United Kingdom). Modulation of PD-1 and PD-L1 expression in response to acute viral infection of human lung tissue. Eur Respir J 2014; 44: Suppl. 58, 3855

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