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The Interaction of Immunodeficiency Viruses with Dendritic Cells

  • R. M. Steinman
  • A. Granelli-Piperno
  • M. Pope
  • C. Trumpfheller
  • R. Ignatius
  • G. Arrode
  • P. Racz
  • K. Tenner-Racz
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 276)

Abstract

Dendritic cells (DCs) can influence HIV-1 and SIV pathogenesis and protective mechanisms at several levels. First, HIV-1 productively infects select populations of DCs in culture, particularly immature DCs derived from blood monocytes and skin (Langerhans cells). However, there exist only a few instances in which HIV-1- or SIV-infected DCs have been identified in vivo in tissue sections. Second, different types of DCs reliably sequester and transmit infectious HIV-1 and SIV in culture, setting up a productive infection in T cells interacting with the DCs. This stimulation of infection in T cells may explain the observation that CD4+ T lymphocytes are the principal cell type observed to be infected with HIV-1 in lymphoid tissues in vivo. DCs express a C-type lectin, DC-SIGN/CD209, that functions to bind HIV-1 (and other infectious agents) and transmit virus to T cells. When transfected into the THP-1 cell line, the cytosolic domain of DC-SIGN is needed for HIV-1 sequestration and transmission. However, DCs lacking DC-SIGN (Langerhans cells) or expressing very low levels of DC-SIGN (rhesus macaque monocyte-derived DCs) may use additional molecules to bind and transmit immunodeficiency viruses to T cells. Third, DCs are efficient antigen-presenting cells for HIV-1 and SIV antigens. Infection with several recombinant viral vectors as well as attenuated virus is followed by antigen presentation to CD4+ and CD8+ T cells. An intriguing pathway that is well developed in DCs is the exogenous pathway for nonreplicating viral antigens to be presented on class I MHC products. This should allow DCs to stimulate CD8+ T cells after uptake of antibody-coated HIV-1 and dying infected T cells. It has been proposed that DCs, in addition to expanding effector helper and killer T cells, induce tolerance through T cell deletion and suppressor T cell formation, but this must be evaluated directly. Fourth, DCs are likely to be valuable in improving vaccine design. Increasing DC uptake of a vaccine, as well as increasing their numbers and maturation, should enhance efficacy. However, DCs can also capture antigens from other cells that are initially transduced with a DNA vaccine or a recombinant viral vector. The interaction of HIV-1 and SIV with DCs is therefore intricate but pertinent to understanding how these viruses disrupt immune function and elicit immune responses.

Keywords

Dendritic Cell Rhesus Macaque Simian Immunodeficiency Virus Productive Infection Human Dendritic 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. M. Steinman
    • 1
  • A. Granelli-Piperno
    • 1
  • M. Pope
    • 2
  • C. Trumpfheller
    • 1
  • R. Ignatius
    • 3
  • G. Arrode
    • 1
  • P. Racz
    • 4
  • K. Tenner-Racz
    • 4
  1. 1.Laboratory of Cellular Physiology and ImmunologyThe Rockefeller UniversityNew YorkUSA
  2. 2.Center for Biomedical ResearchPopulation CouncilNew YorkUSA
  3. 3.Department of Medical Microbiology and Immunology of Infection, Benjamin Franklin Medical CenterFree University of BerlinBerlinGermany
  4. 4.Bernhard Nocht Institute for Tropical MedicineKorber AIDS Research UnitHamburgGermany

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