Effect of tiotropium bromide on expression of CD₈⁺CD₂₅⁺FoxP₃⁺ regulatory T cells in patients with stable chronic obstructive pulmonary disease

Abstract

The expression of CD₈⁺CD₂₅⁺FoxP₃⁺ regulatory T cells (CD₈⁺Tregs) in the peripheral blood of patients with stable chronic obstructive pulmonary disease (COPD), and the effect of muscarinic cholinergic receptor antagonist tiotropium bromide on the expression of CD₈⁺Tregs were investigated. Twenty-three patients with moderate to severe stable COPD were enrolled in this study. All patients inhaled tiotropium bromide (18 μg daily) for 3 months. Before and after inhalation of tiotropium bromide, peripheral blood samples were collected from the patients, and T cells were labeled by three-color labeled monoclonal antibodies. Flow cytometry was used to detect the quantity and percentage of CD₈⁺T cells, CD₈⁺CD²⁵⁺T cells, CD₈⁺Tregs, CD₄⁺T cells, CD₄⁺CD₂₅⁺T cells and CD₄⁺CD²⁵⁺FoxP₃⁺ regulatory T cells (CD₄⁺Tregs) respectively. The percentage of CD₄⁺T cells was increased from (27.82±2.18)% to (35.53±1.3)% (t=3.20, P=0.004) in the peripheral blood of patients with stable COPD after inhalation of tiotropium bromide for 3 months, that of CD₄⁺CD₂₅⁺T cells was decreased from (10.03 ±1.42)% to (4.21 ±0.65)% (t=3.78, P=0.001), and that of CD₈⁺Tregs was increased from (8.41 ±1.68)% to (21.34 ±4.20)% (t=2.72, P=0.013). At baseline, CD₈⁺T cells, CD₈⁺CD₂₅⁺T cells and CD₄⁺Tregs were detectable in the peripheral blood, but no significant changes were observed after treatment. Linear correlation analysis revealed that the difference before and after treatment in CD₄⁺T cells and CD₄⁺CD₂₅⁺T cells was negatively correlated with the ratio of change in CD⁸₊Tregs before and after treatment (r=−0.61, P=0.013; r=-0.72, P=0.001 respectively). In the peripheral blood of patients with stable COPD, there was the expression of CD₈⁺Tregs and CD₄⁺Tregs. Muscarinic receptor antagonist, tiotropium bromide, can promote the amplification of CD₄⁺T cells, inhibit the expression of CD₂₅⁺T cells, and enhance the expression of CD₈⁺Tregs. CD₈⁺Tregs and CD₄⁺Tregs can be used as new indicators to understand the immune status of patients. They are helpful in judging the treatment efficacy and disease immunophenotype.

Keywords

chronic obstructive pulmonary disease / regulatory T cells / tiotropium bromide

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