Biology Reference
In-Depth Information
and interactions of the costimulatory molecules CD80, CD83, and CD86 on
DC provide the necessary signals (signal 2) for e½cient activation of the T cell.
DC also present pathogen-derived peptides on MHC class I molecules to
activate CTL. When DC are themselves infected with viruses, the MHC class
I molecules are loaded in DC similarly as in other cells. The cytosolic viral
proteins synthesized in the DC are processed into peptides and the peptides
are translocated from the cytosol into the endoplasmic reticulum, where they
bind to MHC class I molecules. The peptide-MHC class I complexes are
translocated to the cell surface for scrutiny by CTL. DC are also able to obtain
peptides for MHC class I presentation by processing apoptotic bodies from
infected cells (Mellman et al., 1998).
Thus, the di¨erent forms of DC can be distinguished by di¨erences in cell-
surface expression of molecules involved in these functions ( Fig. 11.2, Table
11.2). Most notably, immature DC express low levels of MHC class II on their
cell surface. In contrast, mature DC express high levels of MHC class II and
costimulatory molecules that are essential for e½cient antigen presentation.
DENDRITIC CELL MIGRATION AND CHEMOKINE ATTRACTION
A central feature of DC is their capacity to migrate. DC progenitors migrate
from blood into peripheral tissues where immature DC act as sentinels against
invading pathogens. Upon pathogen in®ltration, residing immature DC as well
as DC precursors from blood migrate speci®cally to the site of in¯ammation,
sampling foreign antigens. After antigen capture and processing, immature DC
mature and migrate speci®cally to lymphoid tissues through the a¨erent lymph.
In lymphoid tissues, mature DC speci®cally localize in the T-cell areas where
they are ideally positioned to interact with naive T cells and activate antigen-
speci®c T cells (Fig. 11.1).
The nature of the circulating blood cells that give rise to immature DC in
peripheral tissues is unclear. Circulating monocytes represent nonproliferating
precursors that di¨erentiate in vitro to immature DC in the presence of cyto-
kines (Romani et al., 1994; Sallusto et al., 1996). The factors governing the
di¨erentiation in vivo are unclear. It has recently been shown that, after trans-
endothelial migration, monocytes di¨erentiate into immature DC 2 days after
phagocytizing particles, supporting a role for monocytes as blood DC precur-
sors ( Randolph et al., 1998, 1999).
Other populations of possible DC precursors have been identi®ed in periph-
eral blood (Geijtenbeek et al., 2000c; O'Doherty et al., 1994; Weissman et al.,
1995a), which could give rise to immature DC in peripheral tissues. These DC
precursors are present in very low amounts in blood (<0.5% of total peripheral
blood mononuclear cells) and extensive studies are therefore limited by their
paucity. One such DC precursor expresses MHC class II, but lacks the speci®c
lineage markers and surface activation molecules found on other leukocytes,
and is probably en route to becoming tissue DC (O'Doherty et al., 1993; Thomas
