PMID- 12797441 OWN - NLM STAT- MEDLINE DCOM- 20030630 LR - 20190901 IS - 0070-217X (Print) IS - 0070-217X (Linking) VI - 276 DP - 2003 TI - The interaction of immunodeficiency viruses with dendritic cells. PG - 1-30 AB - 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. FAU - Steinman, R M AU - Steinman RM AD - Laboratory of Cellular Physiology and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021-6399, USA. FAU - Granelli-Piperno, A AU - Granelli-Piperno A FAU - Pope, M AU - Pope M FAU - Trumpfheller, C AU - Trumpfheller C FAU - Ignatius, R AU - Ignatius R FAU - Arrode, G AU - Arrode G FAU - Racz, P AU - Racz P FAU - Tenner-Racz, K AU - Tenner-Racz K LA - eng PT - Journal Article PT - Review PL - Germany TA - Curr Top Microbiol Immunol JT - Current topics in microbiology and immunology JID - 0110513 RN - 0 (Antigens, Viral) SB - IM MH - Animals MH - Antigen Presentation/immunology MH - Antigens, Viral/immunology MH - Biological Transport MH - Dendritic Cells/immunology/*virology MH - HIV Infections/immunology/pathology/virology MH - HIV-1/*physiology MH - Humans MH - Monocytes/immunology MH - Simian Immunodeficiency Virus/physiology MH - T-Lymphocytes/immunology/*virology MH - Vaccination RF - 124 EDAT- 2003/06/12 05:00 MHDA- 2003/07/02 05:00 CRDT- 2003/06/12 05:00 PHST- 2003/06/12 05:00 [pubmed] PHST- 2003/07/02 05:00 [medline] PHST- 2003/06/12 05:00 [entrez] AID - 10.1007/978-3-662-06508-2_1 [doi] PST - ppublish SO - Curr Top Microbiol Immunol. 2003;276:1-30. doi: 10.1007/978-3-662-06508-2_1.