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Carl B

Carl Borrebaeck

Professor

Carl B

Genomic and functional delineation of dendritic cells and memory T cells derived from grass pollen-allergic patients and healthy individuals.

Author

  • Malin Lindstedt
  • Åsa Schiött
  • Astrid Bengtsson
  • Kristina Larsson
  • Magnus Korsgren
  • Lennart Greiff
  • Carl Borrebaeck

Summary, in English

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<inf>h</inf>2 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 T<inf>h</inf>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.

Department/s

  • Department of Immunotechnology
  • Department of Translational Medicine
  • Division of Clinical Chemistry and Pharmacology
  • Otorhinolaryngology (Lund)

Publishing year

2005

Language

English

Pages

401-409

Publication/Series

International Immunology

Volume

17

Issue

4

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Medicinal Chemistry
  • Other Clinical Medicine

Status

Published

ISBN/ISSN/Other

  • ISSN: 1460-2377