T-cell polarization depends on concentration of the danger signal used to activate dendritic cells

• Published in: Immunology and cell biology 2010-07, Vol.88 (5), p.537-544
• Main Authors: Peters, Marcus, Dudziak, Karin, Stiehm, Matthias, Bufe, Albrecht
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; allergic immune response; Animals; Cell Separation; dendritic cell; Dendritic Cells - immunology; Female; Flow Cytometry; Interleukin-17 - immunology; lipopolysaccharide; Lipopolysaccharides - immunology; Lymphocyte Activation - immunology; Mice; Mice, Inbred BALB C; OX40 Ligand - biosynthesis; OX40 Ligand - immunology; Respiratory Hypersensitivity - immunology; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Helper-Inducer - immunology; T‐helper cell polarization
• ISSN: 0818-9641; 1440-1711
• DOI: 10.1038/icb.2010.3

Although several studies have focused on allergic sensitization by dendritic cells, to date it is still open under which conditions these antigen‐presenting cells are able to induce an allergic immune response. Our study reveals that BMDCs pulsed with LPS‐free ovalbumine did not induce allergic disease. However, when BMDCs were activated with low‐dose LPS during pulsing with allergen, these cells expressed an inflammatory set of cytokines and co‐stimulatory molecules like CD86 and OX40L. Moreover, activated cells were able to prime mice for massive eosinophilic inflammation of the lung, airway hyper‐reactivity, IgE production and production of Th2 cytokines by lymphocytes. Blocking experiments showed that expression of OX40L is not involved in induction of Th2 response. Interestingly, BMDCs that were activated with high dose of LPS lose their Th2‐sensitizing capacity. Instead these cells induce a Th17 type immune response. We conclude that presentation of allergen by dendritic cells generated with GMCSF is not sufficient to lead to induction of allergic immune response. Further activation of BMDCs is required to prime mice for allergic immune response. In this study, we show that LPS is a suitable stimulus. However, when cells were activated with high dose LPS they tended to induce a Th17 response.