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Plasmacytoid dendritic cells activated by influenza virus and CD40L drive a potent TH1 polarization

Abstract

Plasmacytoid dendritic cells (PDCs) are a subset of dendritic cells present in human blood and inflamed lymph nodes. Here we show that blood PDCs, when stimulated with influenza virus and CD40L in vitro, undergo a maturation process characterized by up-regulation of major histocompatibility complex proteins and adhesion and costimulatory molecules. In addition, PDCs down-regulate CXCR3 and L-selectin, which mediate migration and homing of these cells into the lymph node. Mature PDCs efficiently stimulate T cells and drive a potent TH1 polarization in vitro, which is mediated by the synergistic effect of interleukin 12 and type I interferon. In vivo, mature PDCs are found in secondary lymphoid organs, where they represent the principal source of type I interferon during inflammation. Thus, PDCs probably participate in antiviral and pro-inflammatory responses, rather than in TH2 polarization and tolerance induction.

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Acknowledgements

We thank M. Dessing, T. Hayden and H. Kohler for cell sorting assistance; P. Lane, H. Gallati and I. Julkunen for reagents; M. Kopf, F. Sallusto and R. Ettinger for reading the manuscript. The Basel Institute for Immunology was founded and is supported by Hoffmann-La Roche Ltd, CH-4002 Basel. Part of these results were presented at the Workshop on Lymphoid Organogenesis held in Basel (November 5–6, 1999).

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Correspondence to Marco Colonna.

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Figure 1: Phenotypic analysis of immature and mature PDCs.
Figure 2: T cell stimulatory capacity and morphology of CD40L-matured PDCs.
Figure 3: Viability of DC subsets after stimulation with influenza and intracellular MxA expression.
Figure 4: T cell polarizing capacity of immature or CD40L-stimulated PDCs.
Figure 5: T cell polarizing capacity of immature or influenza virus–stimulated PDCs.
Figure 6: Generation of CD4+ T cells secreting IFN-γand IL-10 by different DC subsets.
Figure 7: Four-color analysis of peripheral blood leukocytes with anti-lineage, anti-CD4, anti-CD11c and anti-ILT3.
Figure 8: PDCs in secondary lymphoid organs.
Figure 9: DC T helper polarizing capacity after cytokine withdrawal.