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噻托溴铵对稳定期慢性阻塞性肺疾病患者CD(8)(+)CD(25)(+)FoxP(3)(+)调节性T细胞表达的影响

Effect of tiotropium bromide on expression of CD(8) (+)CD (25) (+)FoxP (3) (+) regulatory T cells in patients with stable chronic obstructive pulmonary disease.

作者信息

Zhang Jianchu, Deng Li, Xiong Xianzhi, Wang Pei, Xin Jianbao, Ma Wanli

机构信息

Department of Respiratory Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

出版信息

J Huazhong Univ Sci Technolog Med Sci. 2011 Aug;31(4):463. doi: 10.1007/s11596-011-0474-4. Epub 2011 Aug 7.

DOI:10.1007/s11596-011-0474-4
PMID:21823006
Abstract

The expression of CD(8) (+)CD(25) (+)FoxP(3) (+) regulatory T cells (CD(8) (+)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 CD(8) (+)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 CD(8) (+)T cells, CD(8) (+)CD(25) (+)T cells, CD(8) (+)Tregs, CD(4) (+)T cells, CD(4) (+)CD(25) (+)T cells and CD(4) (+)CD(25) (+)FoxP(3) (+) regulatory T cells (CD(4) (+)Tregs) respectively. The percentage of CD(4) (+)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 CD(4) (+)CD(25) (+)T cells was decreased from (10.03 ±1.42)% to (4.21 ±0.65)% (t=3.78, P=0.001), and that of CD(8) (+)Tregs was increased from (8.41 ±1.68)% to (21.34 ±4.20)% (t=2.72, P=0.013). At baseline, CD(8) (+)T cells, CD(8) (+)CD(25) (+)T cells and CD(4) (+)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 CD(4) (+)T cells and CD(4) (+)CD(25) (+)T cells was negatively correlated with the ratio of change in CD(8) (+)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 CD(8) (+)Tregs and CD(4) (+)Tregs. Muscarinic receptor antagonist, tiotropium bromide, can promote the amplification of CD(4) (+)T cells, inhibit the expression of CD(25) (+)T cells, and enhance the expression of CD(8) (+)Tregs. CD(8) (+)Tregs and CD(4) (+)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.

摘要

研究稳定期慢性阻塞性肺疾病(COPD)患者外周血中CD(8)(+)CD(25)(+)FoxP(3)(+)调节性T细胞(CD(8)(+)Tregs)的表达情况,以及毒蕈碱胆碱能受体拮抗剂噻托溴铵对CD(8)(+)Tregs表达的影响。本研究纳入23例中度至重度稳定期COPD患者。所有患者吸入噻托溴铵(每日18μg),共3个月。在吸入噻托溴铵前后,采集患者外周血样本,并用三色标记单克隆抗体标记T细胞。采用流式细胞术分别检测CD(8)(+)T细胞、CD(8)(+)CD(25)(+)T细胞、CD(8)(+)Tregs、CD(4)(+)T细胞、CD(4)(+)CD(25)(+)T细胞和CD(4)(+)CD(25)(+)FoxP(3)(+)调节性T细胞(CD(4)(+)Tregs)的数量和百分比。吸入噻托溴铵3个月后,稳定期COPD患者外周血中CD(4)(+)T细胞百分比从(27.82±2.18)%增至(35.53±1.3)%(t=3.20,P=0.004),CD(4)(+)CD(25)(+)T细胞百分比从(10.03±1.42)%降至(4.21±0.65)%(t=3.78,P=0.001),CD(8)(+)Tregs百分比从(8.41±1.68)%增至(21.34±4.20)%(t=2.72,P=0.013)。基线时,外周血中可检测到CD(8)(+)T细胞、CD(8)(+)CD(25)(+)T细胞和CD(4)(+)Tregs,但治疗后未观察到明显变化。线性相关分析显示,治疗前后CD(4)(+)T细胞和CD(4)(+)CD(25)(+)T细胞的差异与治疗前后CD(8)(+)Tregs的变化比值呈负相关(r=-0.61,P=0.013;r=-0.72,P=0.001)。在稳定期COPD患者外周血中,存在CD(8)(+)Tregs和CD(4)(+)Tregs的表达。毒蕈碱受体拮抗剂噻托溴铵可促进CD(4)(+)T细胞扩增,抑制CD(25)(+)T细胞表达,并增强CD(8)(+)Tregs的表达。CD(8)(+)Tregs和CD(4)(+)Tregs可作为了解患者免疫状态的新指标。它们有助于判断治疗效果和疾病免疫表型。

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