Antigen Presenting Cells (APCs)
397
Tab. 8
T helper cell polarization mediated by DCs.
T
H1
bias
T
H2
bias
Antigen dose
High
Low
Type of antigen
Candida albicans yeast
Toxoplasma
antigen
Candida albicans hyphae
Allergens
Adjuvants
CpG oligonucleotides
LPS
PGE
2
Cholera toxin
MHC-TcR interaction
High afFnity
Short interaction
Low afFnity
Sustained interaction
Stimulator/responser ratio
High
Low
Costimulators
ICAM-1
CD40
OX40-L
ICOS-L
DC state
Mature
Immature
DC type
CD1a
+
(myeloid)
CD1a
(myeloid)
DC localization
Mucosal DC
Cytokine status
High IL-12
Low IL-10
Low IL-12
High IL-10
High IL-6
induce stable IL-12 production by DCs, for
example, high doses of antigen, IFN-
γ
,or
IL-4. Interestingly, monocyte-derived DCs
prime strong T
H1
responses early after
onset of maturation, whereas at later time
points, the same cells prime T
H2
or T
H0
responses. Likewise, when DCs stimulate
naive T cells at low stimulator/responder
ratios, T
H2
polarization is favored despite
th
ep
r
e
s
en
c
eo
fI
L
-
1
2
.R
e
c
en
t
l
y
,i
tw
a
s
proposed
that
different
developmental
lineages of DCs could induce either T
H1
or T
H2
responses, hence the terminology
DC1 or DC2 (Fig. 10) was introduced.
Monocyte-derived or myeloid DCs were
thought to prime T cells towards the
T
H1
phenotype,
whereas
plasmacytoid
DCs were believed to exclusively prime
towards the T
H2
phenotype. However,
this is not the case, as evidenced by
at least two recent observations: CD1a-
negative
subpopulations
of
monocyte-
derived DCs do not secrete IL-12, even
after stimulation with LPS, IFN-
γ
,o
r
CD40L. Likewise, plasmacytoid DCs can
be very potent in priming naive T cells
towards
T
H1
differentiation,
especially
after viral infection.
In conclusion, T helper cell priming
by DCs is very flexible, allowing the
simultaneous generation of T
H1
,T
H2
,and
T
H0
responses.
10.6
Immune Evasion and Plasticity of DCs
In general, DCs, after having met viruses
or other pathogens, will mature and secrete
IL-12, thereby skewing T
H1
differenti-
ation. However, infection of immature
human DCs with herpes simplex virus
type 1 (HSV-1) or vaccinia virus has been
shown to inhibit DC maturation. Likewise,
the bacterial metabolite n-butyrate, which
is found in high concentrations in the
gastrointestinal tract, can interfere with
LPS-induced IL-12 release, but not of IL-10.
IL-10 released during infection with
Borde-
tella pertussis
not only promotes the differ-
entiation of monocytes into macrophages
but also the differentiation of T regula-
tory cells, which suppress protective T
H1
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