RT Journal Article
SR Electronic
T1 Evidence for cell mediated immune dysfunction in the COPD lung: The role of cytotoxic CD4+ T cells
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA2603
DO 10.1183/13993003.congress-2015.PA2603
VO 46
IS suppl 59
A1 Karl J. Staples
A1 Richard T. McKendry
A1 C. Mirella Spalluto
A1 Tom M.A. Wilkinson
YR 2015
UL http://erj.ersjournals.com/content/46/suppl_59/PA2603.abstract
AB COPD patients are susceptible to respiratory viral infection, the mechanisms of immune susceptibility are not known. We recently demonstrated that a subset of CD4+ cells with cytotoxic function correlated with improved clinical outcomes in human volunteers experimentally infected with influenza virus1. The aim of this study was to investigate the presence and function of cytotoxic CD4+ T cells in COPD lung tissue, by investigating the expression of the degranulation marker, CD107a in response to viral infection.Human lung tissue from control or COPD patients undergoing resection surgery was infected with H3N2 X31 Influenza A virus. T cell marker expression was analysed using flow cytometry.The proportion of CD4+ T cells in COPD (mean(SE) 39(2)%) was significantly lower (p=0.016) than in controls (47(3)%), with a corresponding increase in the proportion of CD8+ T cells (31(3)% vs 43(3)%, p=0.004). Influenza infection significantly upregulated expression of CD107a by CD4+ T cells from both controls (75(43) to 210(44) specific mean fluorescence intensity (SMFI), p=0.03) and COPD patients (198(87) to 329(101) SMFI, p=0.03). In contrast, CD8+ T cells from controls could significantly upregulate CD107a expression in response to virus infection (16(16) SMFI to 66(22) SMFI, p=0.03), but not CD8+ cells from COPD patients.These data confirm that there is a proportion of cytotoxic CD4+ T cells in the human lung. A reduction in the number of CD4+ T cells combined with impaired cytotoxic ability of CD8+ T cells in the COPD airway may contribute to the susceptibility of the COPD lung to repeated viral exacerbations.1. Wilkinson et al (2012) Nature Med.