哮喘患者气道调节性T细胞增加

2011/09/08

   背景:哮喘患者中调节性T细胞(T regulatory cells, Tregs)有抑制效应淋巴细胞活性的作用。我们假设Tregs在较重的哮喘患者中会增加。我们也研究通过表达细胞毒性T淋巴细胞抗原4 (CTLA4)的CD4+细胞调控作用,以及上皮内表达CD103的淋巴细胞的数目。
   目的:相比轻度哮喘患者和健康对照组,中重度哮喘患者支气管肺泡灌洗液(BAL)中Tregs的数目。次要目的:研究这些分组中BAL中 CD4+ CTLA4 和 CD4+ CD103 表达。
   方法:用支气管镜检从健康对照受试者(n=6)、轻度哮喘患者(n=15)和中重度哮喘患者(n=13)获得气道淋巴细胞,通过多参数流式细胞分析采用三种方法确定CD4+ Treg细胞数量:CD4+CD25 bright , CD4+CD25+CD127-, and CD4+ FoxP3+
   结果:与轻度哮喘患者(2.5%, P=0.03)和健康受试者(0.95, P =0.003)相比,中重度哮喘患者(4.8%)BAL中CD4+ FoxP3+Tregs百分比增加。CD4+CD25+CD127-Treg 数目有相似的发现,而CD4CD25 bright没有。与轻度哮喘患者和健康对照组比较,中重度哮喘患者CD4 + CTLA4 和 CD103表达增加。
   结论:在中重度哮喘患者中,以FoxP3或CTLA4表达具有调节功能的细胞数量增加。CD4+CD103+上皮内淋巴细胞可保存于组织的炎症部位,这项研究发现显示了这些细胞在哮喘病理生理学的作用。
 
(王刚四川大学华西医院中西医结合科呼吸组 610041 摘译)
                                                (Chest; 2010; 138(4):905–912)
 
 
 
Increased Airway T Regulatory Cells in Asthmatic Subjects

CHEST 2010; 138(4):905–912
 
Background: T regulatory cells (Tregs) may play a role in the suppression of effector lymphocyte activity in asthma.We hypothesized that Treg numbers would be increased in patients with more severe asthma. We also investigated the regulatory function of CD4 cells by expression of cytotoxic T-lymphocyte antigen 4 (CTLA4), and the number of these cells that are intraepithelial lymphocytes expressing CD103.
Objectives: The primary aim was to investigate Treg numbers in the BAL of patients with moderate to severe asthma compared with mild asthma and healthy controls. The secondary aim was to investigate BAL CD4+ CTLA4 and CD4+ CD103 expression in these groups.
Methods: Airway lymphocytes obtained by bronchoscopy from healthy control subjects (six) and patients with mild (15) and moderate to severe (13) asthma were characterized by multiparameter flow cytometric analysis using three methods to determine the numbers of CD4+ Treg cells: CD4+CD25 bright , CD4+CD25+CD127-, and CD4+ FoxP3+.
Results: The % CD4+ FoxP3+Tregs were increased in the BAL of patients with moderate to severe asthma (median 4.8%) compared with both mild asthma patients (median 2.5%, P=.03) and healthy subjects (median 0.95, P =.003). Similar findings were observed for CD4+CD25+CD127-Treg numbers, but not CD4CD25 bright . CD4 + CTLA4 and CD103 expressions were raised in moderate to severe asthma patients compared with those with mild asthma and healthy controls.
Conclusions: The number of cells displaying regulatory capacity, either through FoxP3 expression or CTLA4 expression, is increased in moderate to severe asthma. CD4+CD103+ intraepithelial lymphocytes can be retained at tissue sites of inflammation; our findings indicate a role for these cells in asthma pathophysiology.


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