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特应性哮喘中主要的TH2样支气管肺泡T淋巴细胞群

Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma.

作者信息

Robinson D S, Hamid Q, Ying S, Tsicopoulos A, Barkans J, Bentley A M, Corrigan C, Durham S R, Kay A B

机构信息

National Heart and Lung Institute, London, United Kingdom.

出版信息

N Engl J Med. 1992 Jan 30;326(5):298-304. doi: 10.1056/NEJM199201303260504.

Abstract

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 TH1 and TH2, 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 32P-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 cell that were positive for mRNA for interleukin-2 (P less than 0.05), 3 (P less than 0.01), 4 (P less than 0.001), and 5 (P less than 0.001) and GM-CSF (P less than 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 TH2-like T-cell population.

摘要

背景

在特应性哮喘中,活化的辅助性T淋巴细胞存在于支气管活检标本和支气管肺泡灌洗(BAL)液中,它们产生的细胞因子可能在这种疾病的发病机制中起重要作用。细胞因子释放的不同模式是某些辅助性T细胞亚群的特征,称为TH1和TH2,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产生的模式尚不清楚。

方法

我们通过用32P标记的互补RNA进行原位杂交,评估了轻度特应性哮喘患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信使RNA(mRNA)的表达。通过同时进行原位杂交和免疫荧光以及在T细胞免疫磁珠富集或去除后进行原位杂交,评估mRNA在BAL T细胞中的定位。

结果

与对照受试者相比,哮喘患者每1000个细胞中白细胞介素-2(P<0.05)、3(P<0.01)、4(P<0.001)和5(P<0.001)以及GM-CSF(P<0.001)mRNA阳性的BAL细胞更多。两组之间表达干扰素γmRNA的细胞数量没有显著差异。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。

结论

特应性哮喘与白细胞介素-3、4和5以及GM-CSF基因簇在支气管中的激活有关,这种模式与TH2样T细胞群体的主要激活相一致。

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