Imbalance between Subpopulations of Regulatory T Cells in Patients with Acute Exacerbation of COPD

ABSTRACT

Human regulatory T cells (Tregs) have been reported to be not significantly different in the peripheral blood of patients with chronic obstructive pulmonary disease (COPD) and healthy controls. Recent research has identified some new markers for Tregs and indicated that Tregs are composed of distinct subpopulations. The aim of the study was to describe the changing patterns of circulating Treg subpopulations in patients with acute exacerbation of COPD (AECOPD) and healthy controls, and to explore their potential roles in AECOPD pathogenesis. Blood samples were obtained from 30 never-smokers with normal lung function and 30 patients with COPD before and after they had an exacerbation. The proportions of Treg subpopulations were evaluated using flow cytometry. In the peripheral blood, decreased proportions of CD4⁺CD25⁺CD127^low Tregs, CD4⁺CD25⁺CD45RA⁺ Tregs, and CD4⁺CD25⁺CD62L⁺ Tregs and an increased proportion of CD4⁺CD25⁺CD45RO⁺ Tregs were found in patients with stable COPD compared with non-smokers with normal lung function. The patients showed further changes in Treg subpopulations when they had an AECOPD, with an overall decrease in a suppressive subset, indicating that the immune negative regulatory population of Tregs did not play an effective role. Immune homeostasis favored inflammation, and a negative correlation between the circulating tumor necrosis factor-alpha and the proportions of CD4⁺CD25⁺CD62L⁺ cells (r = −0.698, p < 0.05) in patients with AECOPD was found. The imbalance between the suppressive subsets and the proinflammatory subset of Tregs and the decline of Treg subpopulations with immunosuppressive activity may play important roles in AECOPD progression.

KEYWORDS:

• COPD
• regulatory T cell
• subpopulation
• inflammation

Acknowledgments

The authors thank Guorong Liang, Haijuan Tang, ZhixiuRan and Yi Liang (First Affiliated Hospital of Guangxi Medical University) for their support with screening the participating subjects throughout the study.

Authors' contributions

XY and BH contributed to recruiting the patients, performing all data collection, collecting and processing samples, and writing the manuscript. XZ contributed as primary investigator and was responsible for designing the study and writing the manuscript. WS and WL performed laboratory-based assays. ZH, JD, and JZ recruited the patients and collected clinical data. JB contributed as lead investigator and was responsible for designing the study, analyzing the data, and writing the manuscript. All authors read and approved the final manuscript.

Funding

This work was supported by the National Natural Science Foundation of China (Nos. 81260011 and 30860106) and the Guangxi Natural Science Foundation (No. 2013GXNSFAA019136).

Declaration of interest

None.

Ethical approval

This study is approved by the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University.