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vitro produce a vigorous infection when co-cultured with T cells (Ayehunie et
al., 1995; Cameron et al., 1992b, 1994b; Pope et al., 1994; Weissman et al.,
1995a). Early studies demonstrated that blood DC pulsed with HIV-1 are not
infected themselves, but e½ciently transferred virus to activated T cells. Co-
culture of HIV-1-pulsed DC with activated T cells resulted in an e½cient virus
production, whereas without T cells no virus was produced. Experiments with
di¨erent combinations of human and murine DC or T cells clearly demon-
strated that both human and murine DC could transfer HIV-1 to T cells, but
that human T cells were required for virus production, supporting the model
that T cells are directly infected and that DC facilitate this process (Cameron et
al., 1992b, 1994b). Similar experiments with human skin DC demonstrated that
DC-T cell conjugates were sites of productive virus infection: viral entry into
skin DC was demonstrated by the presence of gag-containing HIV-1 DNA, but
a productive infection only occurred in the presence of T cells. Strikingly, a
productive infection occurred even though the T cells were not activated by
exogenous stimuli, indicating that the presence of DC was su½cient to activate
T cells (Pope et al., 1994) and thus providing a suitable environment for HIV-1
replication.
A model has evolved based on these in vitro data in which DC play an
essential role in HIV-1 capture and viral dissemination upon migration to the
draining lymph nodes to enter the T-cell compartments. Studies of tonsils and
adenoids from several HIV-1-infected patients identi®ed many HIV-1-positive
multinucleated syncytia within the T-cells areas, which contained DC ( Frankel
et al., 1996). These ®ndings represent an in vivo correlation of the permissive
DC±T-cell environment observed in in vitro experiments. Further evidence was
provided by in vivo experiments using simian immunode®ciency virus (SIV )-1.
SIV-rhesus macaque models are being used to further advance our under-
standing of the interactions between DC and HIV-1, and to investigate the in-
volvement of DC in HIV-1 dissemination, especially early after infection. One
such model investigated the infection of tonsils in macaques (Stahl-Hennig et
al., 1999): the strati®ed squamous epithelium overlying the tonsils is compara-
ble to the lining of the vagina and anus, tissues implicated in genital transmis-
sion of HIV-1. Atraumatic application of pathogenic SIV-1 to macaque tonsils
revealed that the infection started locally in the tonsils, but quickly spread to
other lymphoid organs. At day 3, there were few infected cells, but the number
increased rapidly, and reached a plateau after 4 days. The infection was not
detected in the DC-rich squamous epithelium to which the virus was applied,
but was found primarily in CD4
T cells in the T-cell area of tonsils, thus
following the route of migrating DC. Similarly, during acute SIV-1 infection
of macaques, virus replicated primarily in the T-cell areas of lymph nodes
( Reimann et al., 1994). Possibly, DC had captured SIV-1 and carried it to the
T-cell-rich areas for e½cient infection, in accordance with another study in
which rhesus macaques were intravaginally exposed to SIV-1 ( Hu et al., 1999).
SIV entered the vaginal mucosa within 60 min of exposure, infecting primarily
intraepithelial DC, and SIV-infected cells were found in the draining lymph
