Biology Reference
In-Depth Information
a common cell-type: the DC. Various groups have shown that DC residing in
blood, skin, or mucosal surfaces indeed play an important role in this process
(Cameron et al., 1992b; Patterson et al., 1994; Pope et al., 1994; Spira et al.,
1996). Immature DC are the ®rst cells targeted by HIV-1 since they act as sen-
tinels against invading pathogens. DC are directly infected by HIV-1 or capture
the virus, and subsequently transport it from the periphery into the lymphoid
tissues, where DC-bound HIV-1 is transmitted to CD4 T cells, the ultimate
target of HIV-1. Research has mainly focused on studying HIV-1 infection of
CD4 T cells, as the site for viral replication. However, a better understanding
of DC as the initial target for HIV-1 in viral dissemination and chronic infec-
tion, as well as their function in eliciting immunity against HIV-1, is essential
in the successful development of preventative and therapeutic strategies. Re-
cent reviews have extensively described the immunological functions of DC
( Banchereau and Steinman, 1998; Hart, 1997). We will here focus on the facets
of DC biology important in HIV-1 dissemination and pathogenesis and in-
corporate recent ®ndings that shed light on the mechanism by which HIV-1
subverts the migratory and immune function of DC to establish a persistent
infection of CD4 T cells.
DENDRITIC CELLS AS PROFESSIONAL ANTIGEN-PRESENTING
CELLS
DC are professional antigen-presenting cells (APC) that are able to e½ciently
stimulate both naive T and B cells. Both T and B cells need to be activated to
perform their speci®c functions to elicit an e½cient immune response against an
invading pathogen, which ultimately results in clearance of the pathogen and to
antimicrobial resistance. B cells, the precursors of antibody-secreting plasma
cells, directly recognize native antigen presented by DC, which leads to B-cell
activation. In contrast, T cells only recognize peptides bound to major histo-
compatibility complex (MHC) class I and II molecules. Peptides presented by
MHC class I are recognized by cytotoxic CD8 T cells (CTL), whereas peptides
bound by MHC class II interact with helper CD4 T cells. Once activated, the
helper T cells have profound immunoregulatory e¨ects; they interact with
other cells, such as B cells, to induce antibody secretion, macrophages that
subsequently release cytokines, and CTL that destroy pathogen-infected cells.
Activation of naive T cells requires a second signal in addition to the recogni-
tion of peptide-MHC complexes (Mellman et al., 1998); this involves adhesion
and costimulatory molecules, which are essential for prolonged and e½cient
interaction between T cell and DC, resulting in an e½cient immune response.
The professional status of DC as APC is derived from several unique features
( Table 11.1), one of which is its ability to provide signal 2; nonprofessional
APC, like B cells, monocytes, and macrophages, lack the ability to elicit signal
2 and are therefore only capable of stimulating previously activated T cells.
DC progenitors migrate from blood into peripheral tissues, where DC act as
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