Genomic and functional delineation of dendritic cells and memory T cells derived from grass pollen-allergic patients and healthy individuals
Genomic and functional delineation of dendritic cells and memory T cells derived from grass pollen-allergic patients and healthy individuals
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DOI：
10.1093/intimm/dxh220
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发表时间：
2005-04-01
影响因子：
4.4
通讯作者：
Borrebaeck, CAK
中科院分区：
文献类型：
--
作者：
Lindstedt, M;Schiött, Å;Borrebaeck, CAK
树突状细胞 (DCI) 具有调节和激活特定 T 细胞对过敏原反应的强大能力，通过分泌细胞因子和其他介质，在过敏性炎症中发挥关键作用。然而，过敏原攻击的 DC 调节特异性 T 细胞反应的分子机制仍不清楚。本研究旨在利用基因组和功能方法阐明草花粉过敏免疫反应过程中 DC-T 细胞相互作用的分子机制。对草过敏原 Phleum pratense 刺激的 DC 以及与来自健康和过敏供体的过敏原攻击的 DC 共培养的自体记忆 CD4(+) T 细胞进行转录分析。来自过敏供体的 DC 是 T 细胞增殖和 T(h)2 极化的有效诱导剂，如高 IL-4、IL-5 和 IL-13 以及低 IFN-γ 产量所证明的那样。在共培养期间，DC 和 T 细胞上的激活标记物逐渐上调是明显的，这证明了 DC-T 细胞相互作用的教育元素。整体转录分析显示，与健康供体相比，经过敏原刺激后，过敏供体衍生的 DC 和 T 细胞存在差异性基因调控。来自健康和过敏供体的外周记忆CD4(+) T细胞在用负载过敏原的DC刺激后在细胞因子产生、增殖、表面标记表达和基因转录方面也有不同的反应。我们发现与 T(h)2 细胞生物学有关的上调基因，例如对归巢、粘附、信号传导和转录重要的基因，以及以前在过敏背景下未描述的基因。过敏组中差异表达的基因组将为加深对过敏分子机制的了解奠定基础。
Dendritic cells (DCIs) possess a potent ability to modulate and activate specific T-cell responses to allergens, which play a pivotal role in allergic inflammation by secreting cytokines and other mediators. However, the molecular mechanisms by which allergen-challenged DCs regulate specific T-cell responses are still not well characterized. This study aims at elucidating the molecular mechanisms underlying the DC-T-cell interaction during an allergic immune response to grass pollen, using a genomic and functional approach. Transcriptional analysis was performed on grass allergen Phleum pratense-stimulated DCs and on autologous memory CD4(+) T cells co-cultured with allergen-challenged DCs from healthy and allergic donors. DCs from the allergic donors were potent inducers of T-cell proliferation and T(h)2 polarization, as demonstrated by high IL-4, IL-5 and IL-13, and low IFN-gamma production. A gradual up-regulation of activation markers on both DCs and T cells was evident during the co-culture period, demonstrating an educational element of the DC-T-cell interaction. The global transcriptional analysis revealed a differential gene regulation in DCs and T cells derived from allergic donors after stimulation with allergen, as compared with the healthy donors. Peripheral memory CD4(+) T cells from healthy and allergic donors also responded differently after stimulation with allergen-loaded DCs with respect to cytokine production, proliferation, surface marker expression and gene transcription. We found up-regulated genes involved in T(h)2 cell biology, such as genes important for homing, adhesion, signaling and transcription, in addition to genes previously not described in the context of allergy. The panel of differentially expressed genes in the allergic group will form the basis for an increased understanding of the molecular mechanisms in allergy.