       Document 0338
 DOCN  M9630338
 TI    Low levels of HIV-1 infection in cutaneous dendritic cells promote
       extensive viral replication upon binding to memory CD4+ T cells.
 DT    9603
 AU    Pope M; Gezelter S; Gallo N; Hoffman L; Steinman RM; Laboratory of
       Cellular Physiology and Immunology, Rockefeller; University, New York
       10021, USA.
 SO    J Exp Med. 1995 Dec 1;182(6):2045-56. Unique Identifier : AIDSLINE
       MED/96096479
 AB    Earlier work has identified a cell population that replicates HIV-1 in
       the absence of standard T cell stimuli. The system consists of dendritic
       cells and memory T lymphocytes that emigrate from organ cultures of
       human skin and together support a productive infection with HIV-1. These
       emigrants resemble cells that can be found in mucous membranes and that
       normally traffic in afferent lymph. Here, we report that a low level of
       infection in the dendritic cell can initiate extensive HIV-1 replication
       in cocultures with T cells. First we extended our earlier work to larger
       skin specimens from cadavers. As long as the organ cultures were set up
       within 36 h of death, the emigrant leukocytes were comparable to cells
       from fresh surgical specimens in number, phenotype, and function. These
       mixtures of dendritic cells and T cells provided the milieu for a
       productive infection with several virus isolates. When purified
       dendritic cells were separately pulsed with virus and then mixed with T
       cells that had not been pulsed with HIV-1, active infection ensued. The
       infectivity of HIV-pulsed dendritic cells persisted for at least 1.5 d
       in culture, but was blocked if AZT was added during that time to block
       reverse transcription in the dendritic cells. The number of copies of
       proviral DNA in the dendritic cells corresponded to < 100 copies per 5 X
       10(4) cells, but upon mixing with T cells, > 10(4) copies were found 5-7
       d later. By contacting syngeneic T cells, extralymphoid depots of
       dendritic cells--even with a low viral burden as has been reported in
       vivo--may contribute to chronic HIV-1 replication in infected
       individuals.
 DE    Antiviral Agents/PHARMACOLOGY  Cadaver  Cells, Cultured  CD4-Positive
       T-Lymphocytes/*MICROBIOLOGY  CD8-Positive T-Lymphocytes/MICROBIOLOGY
       Dendritic Cells/*MICROBIOLOGY  Human  HIV Infections/*MICROBIOLOGY
       HIV-1/*GROWTH & DEVELOPMENT  Immunologic Memory
       Skin/CYTOLOGY/*MICROBIOLOGY  Support, Non-U.S. Gov't  Support, U.S.
       Gov't, P.H.S.  Virus Replication  Zidovudine/PHARMACOLOGY  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

