Source: International Congress 2015 – Advances from translational research in respiratory infections
Disease area: Airway diseases, Respiratory infections

Abstract

COPD patients are susceptible to recurrent respiratory viral infections which cause disease exacerbations and hasten lung function decline. Mechanisms underlying this susceptibility are not understood. However, CD8+ T cells, are present in increased numbers in COPD patients lungs but fail to resolve infection. We hypothesised that the PD1/PDL1 exhaustion axis, responsible for inhibiting T cell activation, could explain this failure.Human lung tissue explants from control or COPD patients undergoing resection surgery were infected with H3N2 X31 Influenza A virus. Viral infection, PD1 and PDL1 expression was analysed using flow cytometry.The proportion of CD8+ T cells expressing PD1 was significantly greater in COPD (mean(SE) 16.2(4)%) than controls (4.4(1)%, p=0.029). Upon X31 infection, only epithelial cells and macrophages were infected and there was no difference in the proportion of infected cells between controls and COPD. Influenza infection upregulated PD1 expression in controls (p=0.014) and COPD samples (p=0.016). Only macrophages increased PDL1 expression in response to viral infection, but the virus-induced expression of PDL1 was significantly less on COPD macrophages compared to controls (p=0.04). IFNg release into supernatants from infected COPD explants was greater than from controls (86(23) vs 49(22) pg/ml, p=0.04).This work has established a signal of adaptive immune dysfunction in COPD. High PD1 expression on COPD T cells combined with a decreased ability to modulate the activation of these T cells by macrophages, may be a key mechanism explaining both the susceptibility to viral infection and the excessive inflammation which are the drivers to exacerbations.


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Tom Wilkinson (Southampton, United Kingdom), Karl J. Staples, Richard T. McKendry, Hannah Burke, Ben Nicholas, C. Mirella Spalluto, Tom M.A. Wilkinson. Decreased regulation of lung CD8+ T cells by virally-infected macrophages in COPD: Role of PD1/PDL1 axis. Eur Respir J 2015; 46: Suppl. 59, 5031

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