Sileikiene Virginija, Laurinaviciene Aida, Lesciute-Krilaviciene Daiva, Jurgauskiene Laimute, Malickaite Radvile, Laurinavicius Arvydas
Clinic of Chest Diseases, Immunology and Allergology, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
Department of Pathology, Forensic Medicine and Pharmacology, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
Adv Respir Med. 2019;87(3):159-166. doi: 10.5603/ARM.2019.0023.
Many theories have been proposed to explain pathogenesis of COPD; however, remains unclear why the majority of smokers (~80%) do not develop COPD, or only develop a mild disease. To explore if COPD has an autoimmune component, the role of T regulatory lymphocytes (Tregs) in the lung tissue of COPD patients is of crucial importance.
Bronchial tissue biopsy samples were prospectively collected from 64 patients (39 COPD and 25 controls - 15 smokers and 10 non-smokers). The patients with COPD were subdivided into mild/moderate (GOLD stage I-II) and severe/very severe (GOLD stage III-IV) groups. Digital image analysis was performed to estimate densities of CD4+ CD25+ cell infiltrates in double immunohistochemistry slides of the biopsy samples. Blood samples were collected from 42 patients (23 COPD and 19 controls) and tested for CD3+ CD4+ CD25+ bright lymphocytes by flow cytometry.
The number of intraepithelial CD4+ CD25+ lymphocytes mm-2 epithelium was significantly lower in the severe/very severe COPD (GOLD III-IV) group as well as in the control non-smokers (NS) group (p < 0,0001). Likewise, the absolute number of Treg (CD3+ CD4+ CD25+ bright) cells in the peripheral blood samples was significantly different between the four groups (p = 0.032). The lowest quantity of Treg cells was detected in the severe/very severe COPD and healthy non-smokers groups.
Our findings suggest that severe COPD is associated with lower levels of Tregs in the blood and bronchial mucosa, while higher Tregs levels in the smokers without COPD indicate potential protective effect of Tregs against developing COPD.
人们已经提出了许多理论来解释慢性阻塞性肺疾病(COPD)的发病机制;然而,为何大多数吸烟者(约80%)不会患上COPD,或者仅发展为轻度疾病,这仍不清楚。为了探究COPD是否存在自身免疫成分,T调节淋巴细胞(Tregs)在COPD患者肺组织中的作用至关重要。
前瞻性收集了64例患者(39例COPD患者和25例对照者——15例吸烟者和10例非吸烟者)的支气管组织活检样本。COPD患者被分为轻度/中度(GOLD I-II期)和重度/极重度(GOLD III-IV期)组。对活检样本的双重免疫组织化学切片进行数字图像分析,以估计CD4+ CD25+细胞浸润密度。从42例患者(23例COPD患者和19例对照者)采集血样,通过流式细胞术检测CD3+ CD4+ CD25+亮型淋巴细胞。
重度/极重度COPD(GOLD III-IV期)组以及对照非吸烟者(NS)组中,每平方毫米上皮内CD4+ CD25+淋巴细胞数量显著更低(p < 0.0001)。同样,四组外周血样本中Treg(CD3+ CD4+ CD25+亮型)细胞的绝对数量存在显著差异(p = 0.032)。在重度/极重度COPD组和健康非吸烟者组中检测到的Treg细胞数量最低。
我们的研究结果表明,重度COPD与血液和支气管黏膜中较低水平的Tregs相关,而无COPD的吸烟者中较高水平的Tregs表明Tregs对COPD的发生具有潜在保护作用。