T cells expressing the γδ receptor are essential for Th2-mediated inflammation in patients with acute exacerbation of asthma
T cells expressing the γδ receptor are essential for Th2-mediated inflammation in patients with acute exacerbation of asthma
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DOI：
10.1080/09629350220131971
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发表时间：
2002-04-01
影响因子：
4.6
通讯作者：
Hamzaoui, K
中科院分区：
文献类型：
--
作者：
Hamzaoui, A;Kahan, A;Hamzaoui, K
目的：T淋巴细胞在哮喘发病机制中起着中心调节作用。本研究的目的是表征哮喘的免疫激活阶段和诱导痰淋巴细胞的功能特征，特别强调γ - T细胞。方法：收集10例哮喘急性加重期患者及健康对照者的诱导痰。采用双免疫荧光染色和流式细胞术分析新分离的诱导痰淋巴细胞和t细胞亚群活化标志物的表达。采用逆转录-聚合酶链式反应法测定Fas配体（FasL）。采用A13和BB3单克隆抗体检测gd t细胞亚群的表型。在这种情况下，在铬释放试验中测试了γ δ T细胞的功能谱。结果：与健康对照相比，哮喘患者的α - T细胞比例明显降低，γ - T细胞、CD56（+）细胞和CD8(+) γ - T细胞比例明显升高。在哮喘患者中，表达CD69和CD25抗原的T细胞比例显著增加。刺激γ - δ T细胞后，细胞内肿瘤坏死因子-a、白细胞介素(IL)-4和IL - 10细胞因子的表达水平高于对照组。在哮喘患者和健康对照组中观察到相似的干扰素- γ水平。新分离的t细胞受体(TCR) γ δ(+)细胞在我们的患者组中显示出FasL的百分比增加。在IL2刺激前后，TCR γ δ(+)细胞中检测到FasL mRNA。TCR γ δ(+)细胞对K562细胞系具有细胞毒性。这种自然杀伤活性是由a13阳性亚群介导的。结论：哮喘患者诱导痰中存在产生gd细胞的细胞因子，具有一定的调节活性。这些细胞也显示出细胞毒性功能。
OBJECTIVE: T lymphocytes have a central regulatory role in the pathogenesis of asthma. The objective of this study was to characterize immunologically the activation stage of asthma and the functional profile of lymphocytes from induced sputum, with particular emphasis on gammadelta T cells.Methods: Induced sputum was collected from 10 patients with acute exacerbation of asthma, and from healthy controls. The expression of activation markers on freshly isolated induced sputum lymphocytes and T-cell subsets was analyzed by double immunofluorescent staining and flow cytometry. Fas ligand (FasL) was determined by reverse transcriptase-polymerase chain reaction analysis. The phenotype of gd T-cell subpopulations was tested by A13 and BB3 monoclonal antibodies. In this context, the functional profile of gammadelta T cells was tested in a chromium releasing test.Results: A significantly decreased proportion of alphabeta T cells and an increased proportion of gammadelta T cells, CD56(+) cells and CD8(+) gammadelta T cells were found in asthma patients compared with healthy controls. In asthmatic patients, there is a significantly increased proportion of T cells expressing CD69 and CD25 antigen. After stimulation of gammadelta T cells, an increased expression of intracellular tumour necrosis factor-a, interleukin (IL)-4 and IL10 cytokines were found at higher levels than controls. Interferon-gamma was observed at similar levels in asthma patients and healthy controls. Freshly isolated T-cell receptor (TCR) gammadelta(+) cells exhibited an increased percentage of FasL in our patient group. FasL mRNA was detected in TCR gammadelta(+) cells before and after IL2 stimulation. TCR gammadelta(+) cells were cytotoxic against the K562 cell line. This natural killer activity was mediated by the A13-positive subpopulation.Conclusion: The presence of cytokines producing gd cells in induced sputum of asthmatic patients is consistent with regulatory activities. These cells display also cytotoxic function.