Analysis of adaptive CD8+ T cell responses to Influenza A Virus in COPD patients

Abstract

Progression of chronic obstructive pulmonary disease (COPD) is accelerated by exacerbations often caused by viral infections. Here, we examined the systematic immune cell composition of COPD patients and their specific CD8+ T cell response to Influenza A Virus. Whole blood of 31 COPD patients, 47 severe asthma patients and 33 healthy control donors was analyzed by flow cytometry to quantify peripheral immune cell composition and HLA-A2 status. CD8+ T cell numbers and responses specific for HLA-A2-restricted IAV epitopes were determined in peripheral blood mononuclear cells (PBMCs) of these patients using tetramers loaded with conserved IAV epitopes. We confirmed upregulation of innate immune responses in COPD patients as evidenced by elevated numbers of eosinophiles, neutrophiles and monocytes. In contrast, cells of the adaptive immune system, i.e. CD3+ T- and CD19+ B-cells, were significantly reduced in the blood of COPD patients compared to healthy controls and asthma patients. COPD patients showed reduced relative and absolute numbers of CD8+ T cells but not of CD4+ T cells compared to asthma patients suggesting specific alterations in MHC class I-mediated immune responses in COPD. Importantly both, the absolute and the relative number of Influenza A Virus specific CD8+ T cells are diminished in COPD patients compared to healthy controls and asthma patients. We are currently testing the functionality of CD8+ T cells in response to PMA / Ionomycin stimulations in COPD and asthma patients. Our study contributes to an improved understanding of the role of specific anti-viral CD8+ T cell responses in COPD representing a relevant biomarker to identify COPD patients that are prone to frequent exacerbations.