Klein Martin, Plante Sophie, Boulay Marie-Ève, Boulet Louis-Philippe, Chakir Jamila
Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec City, QC, Canada.
Front Allergy. 2023 Dec 1;4:1296601. doi: 10.3389/falgy.2023.1296601. eCollection 2023.
Regulatory T cells (Tregs) contribute to the maintenance of immunological tolerance. There is evidence of impaired function of these cells in people with asthma and allergy. In this study, we evaluated and compared the function of Tregs in allergic asthmatic and allergic non-asthmatic patients, both before and after low-dose allergen challenges.
Three groups of subjects were recruited for a baseline evaluation: healthy controls without allergy or asthma, allergic asthmatic subjects, and allergic non-asthmatic subjects. All of them were subjected to expiratory flow measurements, sputum induction, and blood sampling. In addition, both groups of allergic subjects underwent low-dose allergen challenges. Tregs were isolated from whole blood using CD4CD25 and CD127 staining. The suppression function was measured by flow cytometry. The levels of IL-10, IFN-γ, IgG4, IgA, and TGF-β were measured using ELISA, and sputum Foxp3 was evaluated using qRT-PCR.
The suppressive function of Tregs in healthy controls was significantly higher than in allergic asthmatic or allergic non-asthmatic subjects. Repeated exposure to low doses of allergen increased the suppressor function of Tregs in allergic non-asthmatic subjects but decreased it in allergic asthmatic subjects. Foxp3 gene expression was increased in induced sputum in allergic non-asthmatic subjects, whereas it did not change in asthmatic subjects. Serum IL-10 level was decreased in allergic asthmatic subjects after allergen challenge but not in allergic non-asthmatic subjects. IFN-γ level increased upon allergen challenge in allergic non-asthmatic subjects. IgG4 level was higher in allergic non-asthmatic subjects than in allergic asthmatic subjects.
Low-dose allergen challenges stimulate the suppressor function of Tregs in non-asthmatic allergic subjects but not in allergic asthmatic subjects.
调节性T细胞(Tregs)有助于维持免疫耐受。有证据表明,哮喘和过敏患者体内这些细胞的功能受损。在本研究中,我们评估并比较了过敏性哮喘患者和过敏性非哮喘患者在低剂量过敏原激发前后Tregs的功能。
招募三组受试者进行基线评估:无过敏或哮喘的健康对照者、过敏性哮喘受试者和过敏性非哮喘受试者。所有受试者均进行呼气流量测量、痰液诱导和血液采样。此外,两组过敏受试者均接受低剂量过敏原激发。使用CD4CD25和CD127染色从全血中分离Tregs。通过流式细胞术测量抑制功能。使用酶联免疫吸附测定法(ELISA)测量白细胞介素-10(IL-10)、干扰素-γ(IFN-γ)、免疫球蛋白G4(IgG4)、免疫球蛋白A(IgA)和转化生长因子-β(TGF-β)的水平,并使用定量逆转录聚合酶链反应(qRT-PCR)评估痰液中叉头框蛋白3(Foxp3)的水平。
健康对照者中Tregs的抑制功能显著高于过敏性哮喘患者或过敏性非哮喘患者。反复暴露于低剂量过敏原可增加过敏性非哮喘患者中Tregs的抑制功能,但降低过敏性哮喘患者中Tregs的抑制功能。过敏性非哮喘患者诱导痰液中Foxp3基因表达增加,而哮喘患者中未发生变化。过敏原激发后,过敏性哮喘患者血清IL-10水平降低,但过敏性非哮喘患者未降低。过敏性非哮喘患者过敏原激发后IFN-γ水平升高。过敏性非哮喘患者的IgG4水平高于过敏性哮喘患者。
低剂量过敏原激发可刺激非哮喘性过敏患者中Tregs的抑制功能,但不能刺激过敏性哮喘患者中Tregs的抑制功能。