Department of Immunology and Allergy, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Department of Chest Diseases, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Eur Ann Allergy Clin Immunol. 2021 May;53(3):115-127. doi: 10.23822/EurAnnACI.1764-1489.168. Epub 2020 Sep 11.
CD4T cell subtypes are the central orchestrators of airway inflammation in bronchialasthma (BA); however, the mechanisms that regulate their accumulation in asthmatic airways are still a challenging subject. In addition, neutrophils play a significant role in the development of airway remodeling and their presence may influence clinical presentation of BA being linked to the development of severe BA. Neutrophils have also been found to acquireantigen presenting functions, enabling them to directly activate T cells. The study aimed to evaluate the possible association of chemokine receptor 7 (CCR7) memory CD4T cells andCCR4 effector T cells with disease severity and immunoglobulin E (IgE) production as well as to explore the relationship between these cells and neutrophil function in both allergic andnon-allergic asthmatic patients. Flow cytometry was used to determine the expression of different T cell subset phenotypes (CCR7 memory CD4 and CCR4T cells using anti-human CD3, CD4, CD45RO, CCR4 and CCR7 monoclonal antibodies) utilizing peripheral blood mononuclear cells (PBMCs) isolated from 78 allergic asthmatic patients, 41 non-allergic asthmatic patients, and 40 healthy individuals. Moreover, neutrophils' phagocytic activity was assessed by ingestion of candida particles. We demonstrated increased percentages of CCR7 memory CD4T cells and CCR4CD4T cells in patients compared to control, where this up regulation was significantly higher in allergic than non-allergic asthmatic patients. Additionally, these cells were negatively correlated with improved pulmonary tests and significantly associated with disease severity scores and IgE levels. The neutrophil phagocytic activity was markedly increased in patients compared to control, showing a significant positive correlation with disease severity. . These findings suggest that increased CCR4 CD4 T cells and CCR7 memory CD4 T cells (Tcm) may be associated with BA severity, especially in allergic BA patients and can potentially contribute to the rational design of new therapeutic approaches for asthma in the future.
CD4T 细胞亚群是支气管哮喘(BA)气道炎症的核心调节者;然而,调节它们在哮喘气道中积累的机制仍然是一个具有挑战性的课题。此外,中性粒细胞在气道重塑的发展中起着重要作用,其存在可能影响 BA 的临床表现,并与严重 BA 的发展有关。中性粒细胞也被发现获得了抗原呈递功能,使它们能够直接激活 T 细胞。本研究旨在评估趋化因子受体 7(CCR7)记忆 CD4T 细胞和 CCR4 效应 T 细胞与疾病严重程度和免疫球蛋白 E(IgE)产生的可能相关性,以及探索这些细胞与在过敏性和非过敏性哮喘患者中中性粒细胞功能之间的关系。利用流式细胞术,通过使用抗人 CD3、CD4、CD45RO、CCR4 和 CCR7 单克隆抗体,来确定不同 T 细胞亚群表型(CCR7 记忆 CD4 和 CCR4T 细胞)的表达,利用从 78 名过敏性哮喘患者、41 名非过敏性哮喘患者和 40 名健康个体中分离的外周血单核细胞(PBMCs)。此外,通过吞噬念珠菌颗粒来评估中性粒细胞的吞噬活性。我们发现与对照组相比,患者中 CCR7 记忆 CD4T 细胞和 CCR4CD4T 细胞的百分比增加,其中在过敏性哮喘患者中这种上调更为显著。此外,这些细胞与改善的肺功能测试呈负相关,与疾病严重程度评分和 IgE 水平显著相关。与对照组相比,患者的中性粒细胞吞噬活性显著增加,与疾病严重程度呈显著正相关。这些发现表明,CCR4CD4T 细胞和 CCR7 记忆 CD4T 细胞(Tcm)的增加可能与 BA 的严重程度有关,尤其是在过敏性 BA 患者中,并且可能有助于未来为哮喘设计新的治疗方法。