Lindstedt Malin, Schiött Asa, Bengtsson Astrid, Larsson Kristina, Korsgren Magnus, Greiff Lennart, Borrebaeck Carl A K
Department of Immunotechnology, Lund University, PO Box 7031, S-220 07 Lund, Sweden.
Int Immunol. 2005 Apr;17(4):401-9. doi: 10.1093/intimm/dxh220. Epub 2005 Mar 3.
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.
树突状细胞（DCs）具有调节和激活针对过敏原的特异性T细胞反应的强大能力，这些T细胞通过分泌细胞因子和其他介质在过敏性炎症中起关键作用。然而，过敏原刺激的DCs调节特异性T细胞反应的分子机制仍未得到充分表征。本研究旨在采用基因组和功能方法阐明对草花粉过敏免疫反应期间DC-T细胞相互作用的分子机制。对草过敏原早熟禾刺激的DCs以及与来自健康和过敏供体的过敏原刺激的DCs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DCs是T细胞增殖和T(h)2极化的有效诱导剂，高IL-4、IL-5和IL-13以及低IFN-γ产生证明了这一点。在共培养期间，DCs和T细胞上激活标志物的逐渐上调是明显的，这证明了DC-T细胞相互作用的教育作用。全局转录分析显示，与健康供体相比，来自过敏供体的DCs和T细胞在过敏原刺激后存在差异基因调控。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DCs刺激后，在细胞因子产生、增殖、表面标志物表达和基因转录方面也有不同反应。我们发现了参与T(h)2细胞生物学的上调基因，如对归巢、黏附、信号传导和转录重要的基因，此外还有以前在过敏背景中未描述的基因。过敏组中差异表达基因的面板将为增进对过敏分子机制的理解奠定基础。
