Abstract
To prime immune responses, dendritic cells (DCs) need to be activated to acquire T cell stimulatory capacity. Although some stimuli trigger interleukin 12 (IL-12) production that leads to T helper cell type 1 (TH1) polarization, others fail to do so and favor TH2 polarization. We show that after activation by lipopolysaccharide, DCs produced IL-12 only transiently and became refractory to further stimulation. The exhaustion of cytokine production impacted the T cell polarizing process. Soon after stimulation DCs primed strong TH1 responses, whereas at later time points the same cells preferentially primed TH2 and nonpolarized T cells. These findings indicate that during an immune response, T cell priming conditions may change in the lymph nodes, suggesting another mechanism for the regulation of effector and memory T cells.
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Acknowledgements
We thank M. Lipp and R. Förster for providing antibody to CCR7, H. Kohler, T. Hayden and D. Jarrossay for cell sorting, and I. Giacchetto for technical assistance. The Basel Institute for Immunology was founded and is supported by Hoffmann-La Roche. This work was also supported by Helmut Horten Foundation (to A. Lanzavecchia).
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Langenkamp, A., Messi, M., Lanzavecchia, A. et al. Kinetics of dendritic cell activation: impact on priming of TH1, TH2 and nonpolarized T cells. Nat Immunol 1, 311–316 (2000). https://doi.org/10.1038/79758
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DOI: https://doi.org/10.1038/79758
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