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Kinetics of dendritic cell activation: impact on priming of TH1, TH2 and nonpolarized T cells

Nature Immunology volume 1, pages 311–316 (2000)Cite this article

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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Figure 1: Kinetics of cytokine production in maturing DCs.
Figure 2: Cytokine-producing capacity becomes exhausted following DC maturation.
Figure 3: wConditions favoring TH1 versus TH2 responses.
Figure 4: Correlation of effector function and CCR7 expression in DC priming.
Figure 5: Loss of CCR7 as a function of cell division and DC state.
Figure 6: Effect of duration of T-DC interaction.

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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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Authors and Affiliations

  1. Institute for Research in Biomedicine, Via Vincenzo Vela 6, Bellinzona, CH-6500, Switzerland

    Anja Langenkamp, Mara Messi, Antonio Lanzavecchia & Federica Sallusto

  2. Basel Institute for Immunology, Grenzacherstrasse 487, Basel, CH-4005, Switzerland

    Anja Langenkamp & Federica Sallusto

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  1. Anja Langenkamp
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Correspondence to Federica Sallusto.

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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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