Antigen Presenting Cells (APCs)
389
Tab. 7
Different subsets of human dendritic cells (DCs).
Name
Monocyte-
derived DC
Langerhans
DC
IL-3
receptor
+
DC
Origin
Blood
Bone marrow cord blood
Blood
Precursor
CLA
/CD14
+
CD34
+
/CLA
+
pDC2
Lineage
Myeloid
Plasmacytoid
Plasmacytoid
Phenotype (immature):
MHC class II
++
++
CD207 (Langerin)
−+
+
+
CD11c
++
IL-3 receptor
−−
+
+
CD4
++
+
+
+
apparently
separate
pathways
of
DC
development, which can be distinguished
by the expression of a skin-homing factor,
known as
cutaneous lymphocyte-associated
antigen
(CLA).
One pathway (via CD34
+
/CLA
+
inter-
mediates), depending on TGF-
β
,leadsto
DCs resembling Langerhans cells: they
express the Langerhans cell–associated
antigens Langerin and E-cadherin, CD11c,
CD1a, and have Birbeck granules, char-
acteristic structures known from electron
microscopy studies of Langerhans epider-
mal DCs (Table 7).
The second pathway (via CD34
+
/CLA
,
CD14
+
intermediates, which resemble
blood monocytes) produces DCs reminis-
cent of intestinal DCs (Table 7). They lack
Langerin and E-cadherin, but express the
tetraspanin CD9, the coagulation factor
XIIIa and CD68.
CD14
+
monocyte
pathway
Peripheral
blood monocytes are the most commonly
used precursors for generating human
DCs in culture. CD14
+
monocytes differ-
entiate into DCs (termed DC1) in the pres-
ence of GM-CSF and IL-4. In the presence
of M-CSF, macrophages are generated.
The monocyte-to-DC differentiation can
also be accomplished by seeding mono-
cytes onto a layer of endothelial cells over
a collagen matrix, mimicking the entry
of monocytes into tissues. Most of the
monocytes that have migrated into the col-
lagen matrix remain there and become
macrophages. A subset of them, however,
migrate back through the endothelial bar-
rier and become DCs (Table 7).
Plasmacytoid cell pathway
Human plas-
macytoid cells, termed DC2, were found
by their plasma cell–like morphology and
their unique surface phenotype: they are
strongly positive for the IL-3 receptor,
but negative for CD11c and for myeloid
mineage
markers
(Table 7).
Strikingly,
they produce mRNA for germ-line Ig
κ
and
pre-T-cell receptor
α
. Plasmacytoid cells
are found in blood and many lymphoid tis-
sues. They respond to viral and microbial
stimuli by producing IFN-
α
and IFN-
β
.
10.2
Antigen Uptake Mechanisms
Tissue DCs capture pathogens, infected
cells, dead cells, or their derived products,
and also soluble material to use for antigen
processing and presentation. Importantly,
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