B7 costimulation is required for IL-5 and IL-13 secretion by bronchial biopsy tissue of atopic asthmatic subjects in response to allergen stimulation
B7 costimulation is required for IL-5 and IL-13 secretion by bronchial biopsy tissue of atopic asthmatic subjects in response to allergen stimulation
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DOI：
10.1165/ajrcmb.20.1.3255
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发表时间：
1999-01-01
影响因子：
6.4
通讯作者：
Holgate, S
中科院分区：
文献类型：
--
作者：
Jaffar, Z;Roberts, K;Holgate, S
哮喘是一种复杂的疾病，其特征是气道高反应性和炎症。为了分析支气管粘膜分泌细胞因子所需的细胞相互作用，我们评估了组织外植体对过敏原的体外反应。将来自轻度特应性哮喘受试者和正常对照受试者的支气管内粘膜活检组织维持培养24小时。为了检测对过敏原的反应性，用尘螨提取物屋尘螨 (Der p) 刺激外植体。我们的分析表明，在没有任何明显刺激的情况下，白细胞介素 (IL)-5 和 IL-13 的 mRNA 转录物在哮喘患者而非正常支气管组织中表达。相反，在正常对照受试者的培养支气管活检中观察到干扰素-γ表达的比例高于哮喘受试者的支气管活检。添加 Der p 过敏原并没有改变对照志愿者外植体的细胞因子谱，但增加了 IL-5 mRNA 的表达并诱导哮喘支气管组织分泌该蛋白质。在大多数情况下，过敏原还会增加哮喘受试者支气管组织中 IL-13 的产生。过敏原诱导的 IL-5 和 IL-13 分泌被融合蛋白 CTLA-4Ig 抑制，反映了 Th2 细胞因子表达需要 CD80 (B7-1) 和/或 CD86 (B7-2) 共刺激。这种对 B7/CD28 共刺激的要求与 IL-5 和 IL-13 由哮喘支气管粘膜中的过敏原特异性 T 细胞产生的假设是一致的。
Asthma is a complex disorder characterized by airway hyperreactivity and inflammation. To analyze cellular interactions required for the secretion of cytokines by the bronchial mucosa, we have evaluated the ex vivo response of tissue explants to allergen. Endobronchial mucosal biopsy tissue from mild atopic asthmatic subjects and normal control subjects were maintained in culture for 24 h. To detect reactivity to allergen, the explants were stimulated with dust mite extract Dermatophagoides pteronyssinus (Der p). Our analysis revealed that without any overt stimulation, mRNA transcripts for interleukin (IL)-5 and IL-13 were expressed by asthmatic but not normal bronchial tissue. In contrast, the expression of interferon-gamma was observed in a higher proportion of cultured bronchial biopsies from the normal control subjects than in those from asthmatic subjects. Addition of Der p allergen did not change the cytokine profile of the explants from control volunteers but augmented the expression of IL-5 mRNA and induced secretion of the protein by the asthmatic bronchial tissue. In most cases, allergen also increased the production of IL-13 by bronchial tissue from asthmatic subjects. The allergen-induced secretion of IL-5 and IL-13 was inhibited by the fusion protein CTLA-4Ig, reflecting a requirement for CD80 (B7-1) and/or CD86 (B7-2) costimulation for the for the expression of the Th2 cytokines. This requirement for B7/CD28 costimulation is consistent with the hypothesis that IL-5 and IL-13 are produced by allergen-specific T cells resident in the asthmatic bronchial mucosa.