Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester, Leicester, UK.
Clin Exp Allergy. 2010 Aug;40(8):1175-85. doi: 10.1111/j.1365-2222.2010.03504.x. Epub 2010 Apr 28.
Chemokines and their receptors could play key roles in the recruitment of T cells to the asthmatic lung. CCR8 is preferentially expressed on T-helper type 2 cells, and is thought to play a role in the pathogenesis of human asthma.
Determine the expression of CCR8 on T cells in blood, bronchoalveolar lavage (BAL) and bronchial mucosa from asthmatics and normal subjects.
CCR8 expression in blood and BAL from asthma and normal subjects was studied using flow cytometry. CCR8 expression on IFN-gamma+ and IL-4+/IL-13+ blood and BAL T cells was studied following stimulation with Phorbol-Myristate-Acetate and Calcium Ionophore. Paraffin-embedded bronchial biopsies were used to study CCR8 in bronchial epithelium.
The percentage of CD3+ cells expressing CCR8 in the blood was higher in asthmatics (4.7+/-0.4%) compared with normal subjects (3.0+/-0.4%; P<0.01). There was an approximately sixfold enrichment of CCR8 on IL-4+/IL-13+ cells compared with IFN-gamma+ T cells (P<0.001) in both asthmatic and normal subjects in both blood and BAL. Significantly more BAL T cells expressed CCR8 in asthmatic (8.6+/-0.8%) compared with normal subjects (3.9+/-0.7%) (P<0.01). In paired blood-BAL samples from asthmatics, significantly more CCR8+CD3+ T cells were present in BAL (9.0+/-0.9%) than in blood (5.6+/-0.9%; P<0.05). There were more CCR8-positive cells in bronchial biopsies from asthmatic (93+/-11 cells/mm2) compared with normal subjects (30+/-16 cells/mm2) (P<0.05). The ligand CCL1 was increased in the BAL of asthmatics compared with normal subjects (35+/-6 vs. 12.9+/-7 pg/mL; P<0.05).
There may be a role for CCR8 in the recruitment of T cells to the lung in asthmatics.
趋化因子及其受体可能在 T 细胞募集到哮喘肺中发挥关键作用。CCR8 优先在 Th2 细胞上表达,并且被认为在人类哮喘的发病机制中发挥作用。
确定哮喘患者和正常受试者血液、支气管肺泡灌洗液(BAL)和支气管黏膜中 T 细胞上 CCR8 的表达。
使用流式细胞术研究哮喘患者和正常受试者血液和 BAL 中的 CCR8 表达。在使用佛波醇肉豆蔻酸乙酯和钙离子载体刺激后,研究 IFN-γ+和 IL-4+/IL-13+血液和 BAL T 细胞上的 CCR8 表达。使用石蜡包埋的支气管活检标本研究支气管上皮细胞中的 CCR8。
哮喘患者血液中表达 CCR8 的 CD3+细胞百分比(4.7+/-0.4%)高于正常受试者(3.0+/-0.4%;P<0.01)。在哮喘患者和正常受试者的血液和 BAL 中,与 IFN-γ+T 细胞相比,IL-4+/IL-13+细胞上 CCR8 的富集程度约为六倍(P<0.001)。与正常受试者(3.9+/-0.7%)相比,哮喘患者 BAL 中的 T 细胞表达 CCR8 的比例明显更高(8.6+/-0.8%)(P<0.01)。在哮喘患者的配对血液-BAL 样本中,BAL 中存在的 CCR8+CD3+T 细胞明显多于血液(9.0+/-0.9%比 5.6+/-0.9%;P<0.05)。哮喘患者的支气管活检标本中 CCR8 阳性细胞较多(93+/-11 个细胞/mm2),明显多于正常受试者(30+/-16 个细胞/mm2)(P<0.05)。与正常受试者相比,哮喘患者 BAL 中的 CCL1 增加(35+/-6 比 12.9+/-7 pg/mL;P<0.05)。
CCR8 可能在哮喘患者 T 细胞向肺募集中发挥作用。