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Interplay Between Human Papillomaviruses and Dendritic Cells

  • R. Offringa
  • A. de Jong
  • R. E. M. Toes
  • S. H. van der Burg
  • C. J. M. Melief
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 276)

Abstract

The design of the human papillomavirus (HPV) infection cycle is tightly fitted to the differentiation program of its natural host, the keratinocyte. This has important consequences for the role of antigen-presenting cells in the priming of antiviral immunity. The confinement of HPV infection to epithelia puts the epithelial dendritic cell, the Langerhans cell (LC), in charge of the induction of T cell-dependent immunity. Because HPV-infected keratinocytes cannot reach the regional lymphoid organs, and HPV-infection of LCs does not result in viral gene expression, priming of antiviral T cells exclusively depends on cross-presentation of viral antigens by the LC. Sensitization of the immune system in the regional lymphoid organs elicits systemic anti-HPV immunity as well as intraepithelial immune surveillance by memory-type intraepithelial T cells and locally produced antibodies. The high rate of spontaneous rejections of high-risk HPV-infections and HPV-positive premalignant lesions indicates that in general the LC-driven antigen presentation machinery is capable of raising an effective immune defense against HPV. Epidemiological studies also reveal that a decrease in the vigilance of the immune system is readily exploited by HPV to escape immune destruction, resulting in persistent infections and development of HPVpositive cancers. In view of the inherent antigenicity of HPV, immune intervention strategies constitute a promising approach for both the prevention and the therapeutic treatment of HPV-induced diseases. Importantly, the mechanisms that govern the induction and effector phases of the intraepithelial immune surveillance against HPV must be taken into account when designing such strategies.

Keywords

Dendritic Cell Cervical Intraepithelial Neoplasia Cervical Neoplasia Viruslike Particle Innate Immune Effector Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2003

Authors and Affiliations

  • R. Offringa
    • 1
  • A. de Jong
    • 1
  • R. E. M. Toes
    • 1
  • S. H. van der Burg
    • 1
  • C. J. M. Melief
    • 1
  1. 1.Tumor Immunology Group, Department of Immunohematology and Blood TransfusionLeiden University Medical CenterLeidenThe Netherlands

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