Effect of Tiotropium Bromide on Expression of CD_8~＋CD_（25）~＋FoxP_3~＋ Regulatory T Cells in Patients with Stable Chronic Obstructive Pulmonary Disease

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 immuno