Tsicopoulos A, Janin A, Akoum H, Lamblin C, Vorng H, Hamid Q, Tonnel A B, Wallaert B
INSERM U416 Institut Pasteur de Lille, Clinique des Maladies Respiratoires, Lille, France.
J Allergy Clin Immunol. 2000 Oct;106(4):687-96. doi: 10.1067/mai.2000.109826.
T lymphocytes are important components of the bronchial inflammatory cell infiltrate in asthma. Because lymphocytes activated in the respiratory tract recirculate to remote glandular and mucosal sites, we previously studied the histologic features of minor salivary glands (MSGs) in bronchial asthma and found an airway-like inflammation with T-lymphocyte infiltration, the presence of mast cells that were often degranulated, and basement membrane thickening but no eosinophil infiltration.
We sought to investigate the cellular infiltration and cytokine profile in MSGs from untreated asthmatic subjects, steroid-treated asthmatic subjects, and control subjects and to compare these values with those found in bronchial biopsy specimens.
The cellular infiltration was studied by using immunohistochemistry. Cytokine messenger (m)RNA expression for IL-4, IL-5, and IFN-gamma was determined by using in situ hybridization and cytokine immunoreactivity with immunohistochemistry.
A significant increase in CD4 and IL-4 mRNA(+) cells was observed in MSGs from asthmatic patients (both untreated and steroid-treated subjects) when compared with control subjects, which correlated with the clinical severity of asthma (FEV(1) and Aas score). In contrast to the bronchi, no IL-5 mRNA expression was observed in MSGs, and no difference was observed for MSG IFN-gamma mRNA between the groups. At the level of MSG protein expression, the 3 cytokines were seen, with a significant increase in IL-4 protein expression in steroid-treated asthmatic subjects compared with untreated asthmatic subjects and control subjects, but there were no differences between the groups in IL-5 and IFN-gamma protein expression.
The cytokine mRNA expression pattern observed in the MSGs of asthmatic subjects was different from that found in the bronchi, suggesting a different local immune regulation.
T淋巴细胞是哮喘患者支气管炎性细胞浸润的重要组成部分。由于呼吸道中活化的淋巴细胞会再循环至远处的腺体和黏膜部位，我们之前研究了支气管哮喘患者小唾液腺（MSG）的组织学特征，发现存在类似气道的炎症，伴有T淋巴细胞浸润、常有脱颗粒现象的肥大细胞以及基底膜增厚，但无嗜酸性粒细胞浸润。
我们试图研究未经治疗的哮喘患者、接受类固醇治疗的哮喘患者以及对照受试者的MSG中的细胞浸润和细胞因子谱，并将这些值与支气管活检标本中的值进行比较。
采用免疫组织化学方法研究细胞浸润情况。通过原位杂交和免疫组织化学检测细胞因子免疫反应性，测定白细胞介素-4（IL-4）、白细胞介素-5（IL-5）和干扰素-γ（IFN-γ）的细胞因子信使核糖核酸（mRNA）表达。
与对照受试者相比，哮喘患者（未经治疗和接受类固醇治疗的受试者）的MSG中CD4和IL-4 mRNA(+)细胞显著增加，这与哮喘的临床严重程度（第1秒用力呼气容积（FEV(1)）和哮喘症状评分（Aas评分））相关。与支气管不同，MSG中未观察到IL-5 mRNA表达，且各组间MSG IFN-γ mRNA无差异。在MSG蛋白表达水平上，观察到这3种细胞因子，与未经治疗的哮喘患者和对照受试者相比，接受类固醇治疗的哮喘患者中IL-4蛋白表达显著增加，但各组间IL-5和IFN-γ蛋白表达无差异。
哮喘患者MSG中观察到的细胞因子mRNA表达模式与支气管中不同，提示存在不同的局部免疫调节。
