Analysis of T-cell activation after bronchial allergen challenge in patients with atopic asthma

Analysis of T-cell activation after bronchial allergen challenge in patients with atopic asthma
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DOI:
10.1016/s0091-6749(98)70180-0
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发表时间:
1998-05-01
影响因子:
14.2
通讯作者:
Finn, PW
Finn, PW
中科院分区:
医学1区
文献类型:
--
作者:
Lara-Marquez, ML;Deykin, A;Finn, PW

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背景:辅助性T细胞是一组具有表型和功能差异的异质性细胞。特应性哮喘患者过敏原激发后外周血中存在活化的辅助性T细胞,但特异性T细胞亚群的表型尚不明确。目的:分析特应性哮喘患者过敏原激发前后外周血淋巴细胞的活化情况,探讨可能受过敏原调节的T细胞活化标志物。我们分析了分布的细胞表面活化标志物,白细胞介素2受体(IL-2 R)和主要组织相容性复合物II类抗原(MHC II)之间的T辅助细胞亚群分为幼稚(CD 45 RA)或记忆(CD 45 RO)表型。9例成人特应性哮喘患者接受支气管激发性变应原吸入和等二氧化碳冷空气过度通气(ISH)激发,随后进行连续肺量测定。在基线和攻击后2小时和24小时分离外周血单核细胞(PBMC)。采用四色流式细胞术分析激发后初始和记忆T细胞亚群IL-2 R和MHC LI活化标志物的体内表达和分布。在变应原激发后2和24小时,与基线相比,CD 45 RO +IL-2 R + T辅助细胞显著增加(平均值+/- SE,基线,12.5% +/- 1%对比2小时,18.1% +/- 1%和24小时,17.8% +/-2%,p < 0.025)。在初始和记忆性T辅助细胞上激发后,MHC II表达没有显著增加,并且仅在小比例的CD 45 RO + T辅助细胞(2.7% +/-1%)中发现IL-PR和MHC II的共表达。ISH激发后,IL-2 R和MBC Ⅱ的表达无明显变化。结果表明:在正常人外周血中,有31%~ 46%的T辅助细胞同时表达CD 45 RA和CD 45 RO,且仅表达CD 45 RO的T辅助细胞表达IL-2-R和MHC II。结论:T辅助细胞同时表达CD 45 RA和CD 45 RO,提示外周血中存在幼稚型和记忆型T辅助细胞之间的过渡表型。在特应性哮喘受试者中,我们的体内分析表征了两个群体的激活的记忆性T辅助细胞的基础上表达的IL-2 R或MHC II表面分子过敏原的挑战。
Background: T helper cells are a heterogeneous group of cells that have phenotypic and functional differences. Activated T helper cells have been found in peripheral blood after allergen challenge of subjects with atopic asthma, but the phenotypes of specific T helper subpopulation involved remains to be identified.Objective: To characterize the T cell activation markers that may be regulated by allergens, we analyzed peripheral blood lymphocytes obtained before and after allergen challenge from subjects with atopic asthma.Methods: We analyzed the distribution of the cell surface activation markers, interleukin 2 receptor (IL-2R) and major histocompatibility complex class Ii antigens (MHC II) among T helper subpopulations classified as naive (CD45RA) or memory (CD45RO) phenotypes. Nine adult subjects with atopic asthma underwent bronchoprovacative allergen inhalation and isocapnic cold air hyperventilation (ISH) challenge followed by serial spirometry. Peripheral blood mononuclear cells (PBMC) were isolated at baseline and 2 and 24 hours after challenge. Four color how cytometry was used to analyze the expression and distribution in vivo of IL-2R and MHC LI activation markers on naive and memory T cell subsets after challenge.Results: At 2 and 24 hours after allergen challenge, there was a significant increase in the CD45RO+IL-2R+ T helper cells compared with baseline (mean +/- SE, baseline, 12.5% +/- 1% versus 2 hours, 18.1% +/- 1% and 24 hours, 17.8% +/- 2%, p < 0.025). MHC II expression was not significantly increased after challenge on naive and memory T helper cells and coexpression of IL-PR and MHC II was only found in a small proportion of CD45RO+ T helper cells (2.7% +/- 1%). No changes of IL-2R or MBC II expression on T helper subsets were observed after ISH challenge in the same patients. We also found that 31% to 46% of T helper cells coexpress CD45RA and CD45RO simultaneously, and upregulation of IL-2-R and MHC II expression occurs only on those T helper cells that express CD45RO.Conclusions: We have found that T helper cells express both CD45RA and CD45RO isoforms, which suggests the existence of a transitional phenotype among naive and memory T helper cells in peripheral blood. In subjects with atopic asthma, our in vivo analysis characterizes two populations of activated memory T helper cells based on the expression of IL-2R or MHC II surface molecules after allergen challenge.