Biomedical Engineering Reference
In-Depth Information
Table 3.29.
: decrease;
CTLA: cytotoxic T-lymphocyte antigen; ENTPD: ectonucleoside triphosphate diphosphohy-
drolase; LAG: lymphocyte-activation gene; LAP: latency-associated peptide; NT5E: ecto-5
-
nucleotidase; TGF: transforming growth factor).
T
Reg
cell mechanisms of immunosuppression (Source: [
244
];
↑
: increase;
↓
Mediator
Effect
Contact-dependent suppression
↓
CTLA4
Antigen-presenting cell costimulatory function
,
Interaction with CTLA4 counter-receptor CD80 and CD86 on
conventional T cells
ENTPD, NT5E
Hydrolysis of extracellular ATP
Granzyme-A
Lysis of conventional T cells
LAG3
Inhibitory signaling via MHC class-2 molecules
TNFRSF6
Apoptosis of conventional T cells
Cytokine-mediated suppression
Galectin-1
Cell cycle arrest and apoptosis in conventional T cells
α
IL2R
Adsorption of IL2
↓
IL10
Dendritic cell function
,
Conversion of conventional T cells into T
R1
cells
TGF
β
, LAP
Induction of FoxP3 in conventional T cells
and T
Eff
cells can form immunological synapses with antigen-presenting cells,
where TCR signalosomes are assembled. However, the formation of immunological
synapses with T
Reg
cells is not associated with the recruitment of Src kinases,
protein kinase-C
, and caspase recruitment domain family member CARD11 [
242
].
In addition, T
Reg
cells receive inhibitory signals via TCRs. These receptors activate
protein kinase-B to reduce T
Reg
action. On the other hand, T
Reg
activity is inhibited
by the inflammatory cytokine tumor-necrosis factor-
θ
.
Although T
Reg
and T
Eff
cells have many common signaling components, their
T-cell receptors cause different outcomes. Protein kinase-C
α
θ
is a pro-inflammatory
kinase in both T
Reg
and T
Eff
cells. Whereas PKC
is recruited to the immunological
synapse for full T
Eff
activation, T
Reg
cells exclude it from the synapse to maintain
the suppression against CD4
θ
+
and CD8
+
T
Eff
cells. However, costimulation
enhances PKC
θ
recruitment and lowers immunosuppression, as PKC
θ
precludes
T
Reg
-mediated suppression [
242
].
On
the
other
hand,
PKC
θ
promotes T
Reg
-cell
differentiation via
caspase
recruitment domain (CARD)-containing NF
B activator B-cell lymphoma BCL10
that complexes with Mucosa-associated lymphoid tissue lymphoma translocation
peptidase MALT1 and CARD-containing protein of the MAGUK family CARD11
[
241
]. T
Reg
-cell differentiation is promoted by the TCR-activated NF
κ
κ
B pathway
and the IL2-STAT5 axis, but hindered by the PKB-TOR pathway.
Regulatory T cells can have several basic modes of immunosuppressive action
(Table
3.29
)[
243
]: (1) release of inhibitory cytokines, such as interleukin-10 and -
35 and transforming growth factor-
β
; (2) cytolysis via granzyme and perforin, e.g.,
CD4
(PTPRc
hMW
)
regulatory T cells stimulated with CD3- (CD3: signaling component of the T-cell
+
(CD4: coreceptor for MHC class-2 molecules), CD45Ra
+
Search WWH ::
Custom Search