Systemic CD4+ and CD8+ T-cell cytokine profiles correlate with GOLD stage in stable COPD

Abstract

Chronic obstructive pulmonary disease (COPD) is associated with pulmonary and systemic inflammation. Both CD4+ and CD8+ T-lymphocytes play a key role in COPD pathogenesis, but cytokine profiles in circulating T-lymphocytes have not been well characterised.Here we report the analysis of peripheral blood T-cells from 30 stable COPD patients and 10 healthy never-smokers for interferon (IFN)-c, interleukin (IL)-4, tumour necrosis factor (TNF)-a and the T-helper 17 cytokines IL-17A, IL-17F and IL-22 by intracellular flow cytometry.We found significantly increased proportions of IFN-c+ and TNF-a+ CD8+ T-cells in COPD patients, when compared with healthy controls. This was most evident in patients with less severe disease. In contrast, expression profiles in circulating CD4+ T-cells were similar in COPD patients and healthy controls for all cytokines tested, except for IL-17F. COPD patients with more severely reduced diffusing capacity had lower proportions of IL-17A+ CD4+ T-cells. Proportions of IL-22+ cells in the CD4+ memory T-cell population were significantly increased in active smokers, when compared with past smokers.Collectively, this comprehensive cytokine analysis of circulating T-cells in COPD patients revealed a correlation for CD8+ T-cells between Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and IFN-c or TNF-a expression, but not for CD4+ T-cells.

Basal Gene Expression by Lung CD4+ T Cells in Chronic Obstructive Pulmonary Disease Identifies Independent Molecular Correlates of Airflow Obstruction and Emphysema Extent

“…The ultimate molecular bases for these dysfunctional lung CD4+ T cell phenotypes remain uncertain. Some recent evidence supports a systemic defect of CD4+ T cell polarization in COPD [31], but we currently favor a specific effect of the lung environment uniquely affecting lung CD4+ T cells for the loss of polarization (Group A) phenotype.…”

“…First, CD8+ T cells might still receive adequate help in regional lymph nodes if defective production of inflammatory cytokines by CD4+ T cells in COPD were limited to the lungs, but that possibility has recently been questioned [31]. Additionally, CD4-independent CD8+ T cells responses have been observed in tumors and several infectious diseases [54].…”

T helper 17 cells are involved in the local and systemic inflammatory response in community-acquired pneumonia

“…Levels of IL-17 were below detection in both compartments 22. IL-22 levels in serum, but not in BAL fluid, were significantly higher in CAP patients compared with healthy individuals (see online supplementary figure S3).…”

“…Cells were stained as described previously22 and measured on a LSRII Flowcytometer (BD Biosciences). Data were analysed using FlowJo (BD) software.…”

Mode of dendritic cell activation: The decisive hand in Th2/Th17 cell differentiation. Implications in asthma severity?

“…Furthermore, cigarette smoking COPD patients show increased levels of IL-22 in serum and IL-17 and IL-22 in sputum. This implies that cigarette smoke specifically leads to increased expression of Th17 cell cytokines (Paats et al 2012;Zhang et al 2013).…”