International Immunology Advance Access originally published online on March 3, 2005
International Immunology 2005 17(4):401-409; doi:10.1093/intimm/dxh220
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Genomic and functional delineation of dendritic cells and memory T cells derived from grass pollen-allergic patients and healthy individuals
1 Department of Immunotechnology, Lund University, PO Box 7031, S-220 07 Lund, Sweden
2 SIK, Swedish Institute for Food and Biotechnology, S-223 70 Lund, Sweden
3 Department of Clinical Pharmacology and 4 Department of Otorhinolaryngology, Lund University Hospital, S-221 85 Lund, Sweden
Correspondence to: C. A. K. Borrebaeck; E-mail: carl.borrebaeck{at}immun.lth.se
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 Th2 polarization, as demonstrated by high IL-4, IL-5 and IL-13, and low IFN-
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 Th2 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.
Keywords: allergen, gene expression profiling, hay fever, Phleum, Th2 cells
Transmitting editor: K. Takatsu
* These authors contributed equally to the experimental work of this article.
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