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where pathogens must be captured. It has recently been shown that the HIV-1
envelope glycoprotein gp120 can also induce a chemotactic response in imma-
ture DC via CCR5, resulting in speci®c migration toward HIV-1 in vitro (Lin
et al., 2000). The CXC chemokines mediate the second stage in the DC-speci®c
migration process, from in¯amed tissues through the lymphatics and to the
T-cell areas of the lymph nodes. The migrating DC are maturing and down-
regulate CCR1 and CCR5, but up-regulate receptors for constitutive chemo-
kines such as CXCR4 and CCR7 (Sallusto et al., 1998), whose chemokines,
SDF-1 and SLC, are expressed in lymphoid tissues. Thus, the rapid and strict
regulation of chemokine receptor expression on DC, depending on their di¨er-
entiation stage, plays a vital role in the migratory capacity of DC.
EXPRESSION OF HIV-1 RECEPTORS ON DC
Three distinct HIV-1 receptors are expressed on DC: CD4, the chemokine re-
ceptors CCR5 and CXCR4, and DC-SIGN. CD4 and the chemokine receptors
are also found on T cells, B cells, and monocytes, but the recently identi®ed
HIV-1 gp120-binding receptor DC-SIGN is expressed only on DC (Fig. 11.3A)
(Geijtenbeek et al., 2000a, b). The primary HIV-1 receptor CD4 has been de-
tected on di¨erent DC populations, albeit at lower levels than on CD4
T cells
(Granelli-Piperno et al., 1996; Rubbert et al., 1998). CD4
DC populations
have been identi®ed in blood (Weissman et al., 1995a) and in vivo in mucosal
tissues that are involved in sexual HIV-1 transmission, such as cervix and uter-
us. Langerhans cells, the DC population that resides in the skin epidermis as
well as in the mucosal epithelium, are also positive for CD4 (Wood et al.,
1983).
The chemokine receptors CCR5 and CXCR4 have been identi®ed as the
predominant receptors for HIV-1 entry into target CD4
T cells ( Littman,
1998). The primary coreceptor for M-tropic HIV-1 is CCR5 (Alkhatib et al.,
1996; Choe et al., 1996; Deng et al., 1996), whereas CXCR4 is the coreceptor
for T-tropic HIV-1 (Feng et al., 1996). The natural ligands of these HIV-1
coreceptors, the in¯ammatory chemokines RANTES, MIP-1a, MIP-1b (Com-
badiere et al., 1996; Samson et al., 1996) and SDF-1, prevent infection by ob-
structing HIV-1 env-mediated membrane fusion and thus viral entry (Alkhatib et
al., 1996; Bleul et al., 1996; Deng et al., 1996). Predominantly M-tropic HIV-1
strains are responsible for the initial dissemination events after sexual transmis-
sion of the virus; the location of DC in the peripheral mucosal tissues has greatly
enhanced the study of their involvement in the selection of only M-tropic HIV-1
strains, and the predominant expression of CCR5 on DC has therefore been of
particular interest. Expression of both CCR5 and CXCR4 has been detected on
in vitro cultured DC, but the expression of both depends on the maturation
state, DC subtype, and manner of isolation; variations are observed between
DC studied in vitro and in vivo. Both blood- and monocyte-derived DC express
CCR5 and CXCR4 (Ayehunie et al., 1997; Delgado et al., 1998; Dittmar et al.,
