388
Antigen Presenting Cells (APCs)
different murine lymphoid tissues and the
expression of distinct markers not present
on human DCs. Hence, there was evi-
dence that the CD8
+
DCs of the thymus
shared early steps of development with T
cells. They were thought to derive from
lymphoid-restricted precursors and were
named
lymphoid DCs
.A
l
lo
the
rDC
sbe
-
ing CD8
were thought to originate from
myeloid-restricted precursors; they were
called
myeloid DCs
. In the meantime, when
myeloid- and lymphoid-restricted precur-
sors were isolated from bone marrow,
it became evident that each precursor
could produce all the mature splenic and
thymic DC subtypes. Besides CD8 and
CD4, the integrin
α
M
chain (CD11b), the
lectin DEC205 (CD205) and the integrin
α
X
chain (CD11c) are used as surface mark-
ers to distinguish murine DC subtypes.
Currently, the terms
myeloid
and
plasma-
cytoid
(Table 6) are used to distinguish DC
lineages in both mouse and man.
10.1.2
Human DC Subtypes
In contrast to the situation in mice,
only blood and bone marrow can be
used as an
ex vivo
source of human
DCs.
Human
blood
DCs
are
highly
heterogeneous in their marker expression,
with many markers reflecting differences
in the maturation or activation state rather
than separate lineages. A comparison to
mouse subtypes is difFcult, since human
DCs lack expression of CD8. Only human
thymic DCs make a strong case for subset
segregation, similar to that in mouse: most
human thymic DCs are CD11c
+
CD11b
and lack myeloid markers, and so resemble
murine thymic CD8
+
DCs.
As yet, most insight into DC subsets has
come from studies of their development in
culture from precursors. Essentially three
distinct precursor types have been used:
CD34
+
bone marrow–derived precursors,
blood monocytes, and plasmacytoid cells
(Table 7).
CD34
+
precursor pathway
The earliest
precursors used are CD34
+
and derived
from
bone
marrow
or
umbilical-cord
blood. Liquid culture with granulocyte-
macrophage
colony-stimulating
factor
(GM-CS±)
and
TN±-
α
leads
to
two
Tab. 6
Tissue distribution of murine DC subtypes.
Tissue
Percentage of total DCs
a
Myeloid DCs
Plasmacytoid DCs
CD4
+
CD8
CD205
CD11b
+
CD4
CD8
CD11b
+
CD4
CD8
+
CD205
+
CD11b
lymphoid
CD4
CD8
+
CD205
+
CD11b
+
Langerhans DCs
Spleen
56
20
23
<
1
Thymus
60
Mesenteric
lymph nodes
46
31
9
<
4
Skin-draining
lymph nodes
43
71
73
3
a
Adapted from Shortman, K., Lin, Y.J. (2002)
Nature Reviews
2
, 151–161.
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