Role of Regulatory T Cells in Chronic Obstructive Pulmonary Disease

TL;DR

This study explores how regulatory T cells function in COPD patients, finding impaired suppression and altered cytokine levels compared to healthy individuals.

Contribution

The study reveals compromised Treg function in COPD patients, particularly in smokers and reformed smokers, offering new insights into the disease's immune mechanisms.

Findings

COPD patients showed significantly lower Treg suppression of T responder cells compared to controls.

COPD smokers had reduced IL-2, IL-10, and TGF-β1 levels in suppression assays compared to other groups.

COPD smokers exhibited a higher frequency of iTregs with a specific phenotype compared to reformed smokers.

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder characterized by poorly reversible airway obstruction. COPD being an inflammatory disorder has been proposed to have an imbalance between proinflammatory and anti-inflammatory factors. Regulatory T cells (Tregs) being a negative regulator of immune response have been observed to play an important role in other inflammatory diseases as well as animal models of inflammation.

Objective: This study is aimed at assessing the suppressive functions of circulatory Tregs and examining the inductive capacity of naive CD4+ T cells to generate induced Tregs.

Methods: The study was conducted in 20 COPD patients (smokers n = 10; reformed smokers n = 10) and 20 age-matched healthy controls (smokers n = 10; nonsmokers n = 10). Peripheral blood mononuclear cells were isolated from blood using Ficoll density gradient separation. The suppressive functions were evaluated by assessing the proliferation of T responder cells (CD4+CD25−) in the presence of circulatory Tregs (CD4+CD25+) under polyclonal stimulation. In addition, cytokine-mediated suppression was assessed in the culture supernatants of the suppression assay. Inductive capacity was assessed by stimulating naive CD4+ T cells to generate iTregs in the presence of anti-CD3, IL-2, and TGF-β1.

Results: The percent suppression of T responder cells by Tregs was significantly lower in COPD smokers (p = 0.03) and COPD reformed smokers (p = 0.04) as compared to control smokers. On the assessment of cytokine-mediated suppression, significantly reduced IL-2 in COPD S as compared to COPD RS (p < 0.05) and reduced IL-10 and TGFß1 in COPD S as compared to CNS (p < 0.05) and CS (p < 0.05) was observed in the culture supernatants of suppression assay. In addition, a significantly higher frequency of iTregs with phenotype CD4+CD25+CD45RA+CD127− was observed in COPD S as compared to COPD RS (p < 0.01).

Discussion: Characteristics changes were observed in patients with COPD. The compromised Tregs function, despite the increase in systemic inflammation, suggests a potential role of these cells in the pathogenesis of the disease.

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