Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to eosinophilic airway inflammation
Bart N. Lambrecht, … , Kris Thielemans, Romain A. Pauwels
Bart N. Lambrecht, … , Kris Thielemans, Romain A. Pauwels
Published August 15, 2000
Citation Information: J Clin Invest. 2000;106(4):551-559. https://doi.org/10.1172/JCI8107.
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Article

Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to eosinophilic airway inflammation

Abstract

The aim of this study was to investigate whether dendritic cells (DCs) can induce sensitization to aeroallergen in a mouse model of allergic asthma. Ovalbumin-pulsed (OVA-pulsed) or unpulsed myeloid DCs that were injected into the airways of naive mice migrated into the mediastinal lymph nodes. When challenged 2 weeks later with an aerosol of OVA, activated CD4 and CD8 lymphocytes, eosinophils, and neutrophils were recruited to the lungs of actively immunized mice. These CD4+ lymphocytes produced predominantly IL-4 and IL-5 but also IFN-γ, whereas CD8+ lymphocytes produced predominantly IFN-γ. Histological analysis revealed perivascular and peribronchial eosinophilic infiltrates and goblet cell hyperplasia. Studies in IL-4–/– and CD28–/– mice revealed that production of IL-4 by host cells and provision of costimulation to T cells by DCs were critical for inducing the response. Lung CD4+ T cells strongly expressed the Th2 marker T1/ST2, and signaling through this molecule via a ligand expressed on DCs was essential for the establishment of airway eosinophilia. These data demonstrate that DCs in the airways induce sensitization to inhaled antigen and that molecules expressed on the surface of these cells are critical for the development of Th2-dependent airway eosinophilia.

Authors

Bart N. Lambrecht, Marijke De Veerman, Anthony J. Coyle, Jose-Carlos Gutierrez-Ramos, Kris Thielemans, Romain A. Pauwels

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Figure 6

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(a) T1/ST2 expression on BALF cells. Mice were immunized with OVA-DC and...
(a) T1/ST2 expression on BALF cells. Mice were immunized with OVA-DC and subsequently challenged with OVA as described in Methods. Control mice (PBS) were immunized with PBS-DC and challenged with PBS. Single-cell suspensions were surface stained with mAb’s against CD3, CD4, and T1/ST2. Dot plots were gated on CD3+ viable lymphocytes. The percentage of CD4+ lymphocytes expressing T1/ST2+ is indicated. (b) Expression of a putative ligand for T1/ST2 on mouse DCs. Bone marrow DCs were stained for CD11c, MHC class II, and T1/ST2-Ig, followed by secondary anti–hu-Ig-FITC. As a control, staining was performed using hu-Ig as primary antibody (broken line). Histogram was gated on CD11c+ MHC class II+ cells and is representative of three separate experiments.