Lack of allergy to timothy grass pollen is not a passive phenomenon but associated with the allergen-specific modulation of immune reactivity.
Lack of allergy to timothy grass pollen is not a passive phenomenon but associated with the allergen-specific modulation of immune reactivity.
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DOI：
10.1111/cea.12692
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发表时间：
2016-05
期刊：
影响因子：
--
通讯作者：
Sette A
中科院分区：
文献类型：
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作者：
Hinz D;Seumois G;Gholami AM;Greenbaum JA;Lane J;White B;Broide DH;Schulten V;Sidney J;Bakhru P;Oseroff C;Wambre E;James EA;Kwok WW;Peters B;Vijayanand P;Sette A
蒂莫西草（TG）花粉是一种常见的季节性空气过敏原，与从轻度鼻炎到严重哮喘的症状有关。本研究的目的是描述TG特异性T细胞反应随季节性变化的特征。外周血单核细胞（PBMC）从过敏性个人和非过敏性对照，无论是在花粉季节或淡季，刺激TG提取物或池先前确定的免疫显性抗原区域。来自过敏受试者的PBMC在季节中比在季节外收集时表现出更高的IL-5和IL-10应答。在非过敏性受试者的情况下，正如预期的那样，我们观察到与过敏性个体相比，IL-5应答较低，IFNγ的产生较强。引人注目的是，非过敏性供体表现出相反的模式，季节性免疫反应性降低。非过敏供体中的广泛下调表明，健康个体并没有忘记过敏原暴露，而是在花粉季节提供抗原刺激后对反应进行主动调节。过敏原特异性T细胞的转录组学分析确定了在非过敏供体中伴随过敏原暴露和反应抑制而调节的基因。在过敏性和非过敏性受试者中，T辅助细胞反应的幅度和功能在季节内与季节外有很大不同。结果表明，在花粉季节的抗原刺激后的免疫反应的具体和相反的调制。这种季节性调节反映了与健康和过敏性疾病相关的特定分子程序的制定。
Timothy grass (TG) pollen is a common seasonal airborne allergen associated with symptoms ranging from mild rhinitis to severe asthma. The aim of this study was to characterize changes in TG-specific T cell responses as a function of seasonality. Peripheral blood mononuclear cells (PBMC) obtained from allergic individuals and non-allergic controls, either during the pollen season or out-of-season, were stimulated either with TG extract or a pool of previously identified immunodominant antigenic regions. PBMC from allergic subjects exhibit higher IL-5 and IL-10 responses in-season than when collected out of season. In the case of non-allergic subjects, as expected we observed lower IL-5 responses and robust production of IFNγ compared to allergic individuals. Strikingly, non-allergic donors exhibited an opposing pattern, with decreased immune reactivity in-season. The broad downregulation in non-allergic donors indicates that healthy individuals are not oblivious to allergen exposure but rather react with an active modulation of responses following the antigenic stimulus provided during the pollen season. Transcriptomic analysis of allergen-specific T cells defined genes modulated in concomitance with allergen exposure and inhibition of responses in non-allergic donors. Magnitude and functionality of T-helper cell responses differ substantially in-season versus out-of-season in allergic and non-allergic subjects. The results indicate specific and opposing modulation of immune responses following the antigenic stimulation during the pollen season. This seasonal modulation reflects the enactment of specific molecular programs associated with health and allergic disease.