PREDOMINANT TH2-LIKE BRONCHOALVEOLAR LYMPHOCYTE-T POPULATION IN ATOPIC ASTHMA
PREDOMINANT TH2-LIKE BRONCHOALVEOLAR LYMPHOCYTE-T POPULATION IN ATOPIC ASTHMA
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DOI：
10.1056/nejm199201303260504
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发表时间：
1992-01-30
影响因子：
158.5
通讯作者：
KAY, AB
中科院分区：
文献类型：
--
作者：
ROBINSON, DS;HAMID, Q;KAY, AB
背景在特应性哮喘中，活化的T辅助淋巴细胞存在于支气管活检标本和支气管肺泡灌洗液（BAL）中，它们产生的细胞因子可能在这种疾病的发病机制中很重要。不同的细胞因子释放模式是T辅助细胞的某些亚群的特征，称为T（H1）和T（H2），前者介导迟发型超敏反应，后者介导IgE合成和嗜酸性粒细胞增多。特应性哮喘中细胞因子的产生模式尚不清楚。我们通过与P-32标记的互补RNA原位杂交，评估了轻度特应性哮喘受试者和正常对照受试者BAL获得的细胞中白细胞介素-2，3，4和5，粒细胞-巨噬细胞集落刺激因子（GM-CSF）和干扰素γ的信使RNA（mRNA）的表达。通过同时原位杂交和免疫荧光以及免疫磁性富集或去除T细胞后原位杂交评估mRNA在BAL T细胞中的定位。与对照组相比，哮喘组每1000个BAL细胞中IL-2（P < 0.05）、IL-3（P <0.01）、IL-4（P <0.001）、IL-5（P <0.001）和GM-CSF（P < 0.001）mRNA阳性细胞数明显增多。两组间表达干扰素γ mRNA的细胞数量无显著差异。在哮喘患者中，白细胞介素4和5的mRNA主要由T淋巴细胞表达。特应性哮喘与支气管中白细胞介素3、4和5以及GM-CSF基因簇的激活相关，这种模式与T（H2）样T细胞群的主要激活相一致。
Background. In atopic asthma, activated T helper lymphocytes are present in bronchial-biopsy specimens and bronchoalveolar-lavage (BAL) fluid, and their production of cytokines may be important in the pathogenesis of this disorder. Different patterns of cytokine release are characteristic of certain subgroups of T helper cells, termed T(H1) and T(H2), the former mediating delayed-type hypersensitivity and the latter mediating IgE synthesis and eosinophilia. The pattern of cytokine production in atopic asthma is unknown.Methods. We assessed cells obtained by BAL in subjects with mild atopic asthma and in normal control subjects for the expression of messenger RNA (mRNA) for interleukin-2, 3, 4, and 5, granulocyte-macrophage colony-stimulating factor (GM-CSF), and interferon gamma by in situ hybridization with P-32-labeled complementary RNA. Localization of mRNA to BAL T cells was assessed by simultaneous in situ hybridization and immunofluorescence and by in situ hybridization after immunomagnetic enrichment or depletion of T cells.Results. As compared with the control subjects, the subjects with asthma had more BAL cells per 1000 cells that were positive for mRNA for interleukin-2 (P < 0.05), 3 (P < 0.01), 4 (P < 0.001), and 5 (P < 0.001) and GM-CSF (P < 0.001). There was no significant difference between the two groups in the number of cells expressing mRNA for interferon gamma. In the subjects with asthma, mRNA for interleukin-4 and 5 was expressed predominantly by T lymphocytes.Conclusions. Atopic asthma is associated with activation in the bronchi of the interleukin-3, 4, and 5 and GM-CSF gene cluster, a pattern compatible with predominant activation of the T(H2)-like T-cell population.