Biomedical Engineering Reference
In-Depth Information
Table 3.30.
Development and phenotype of regulatory T cells (T
Reg
; Source: [
245
]; MALT:
mucosa-associated
lymphoid
tissue T
R1
: type-1
regulatory
T lymphocyte;
iT
Reg
:
inducible
T
Reg
lymphocyte; nT
Reg
: natural T
Reg
lymphocyte). Forkhead box FoxP3
T
Reg
cells are potent
mediators of self tolerance, thereby preventing autoimmunity. They promote cancer progression
when they repress antitumor immunity. In humans, T
Reg
+
cells have diverse functions and
phenotypes.
Locus
Progenitor
Produced cells
+
Thymus
Uncommitted thymocyte
CD4
thymocyte
CD8
+
thymocyte
CD4
+
thymocyte
CD4
+
FoxP3
+
nT
Reg
Periphery
CD4
+
naive T cell
CD4
+
FoxP3
+
iT
Reg
CD8
+
naive T cell
CD8
+
FoxP3
+
/−
T
Reg
MALT
CD4
+
naive T cell
CD4
+
FoxP3
+
iT
Reg
TGF
-secreting T
Reg
(T
H
3)
IL10-secreting T
Reg
(T
R1
)
β
receptor complex) and CD46-specific (CD46: ubiquitous inhibitory complement
receptor) antibodies; (3) apoptosis mediated by cytokine deprivation that depends
on IL2 receptor-
(or CD25); (4) cell inhibition by intracellular transfer of
cAMP through gap junctions; (5) immunosuppression via A
2
adenosine receptor
stimulated by pericellular generation of adenosine due to concordant action of
ectoenzymes — ectonucleoside triphosphate diphosphohydrolase ENTPD1 (or
CD39) and ecto-5
-nucleotidase (NT5E or CD73); (6) inhibition of dendritic cell
maturation by lymphocyte-activation gene product LAG3 (or CD223) that binds
to MHC class-2 molecules and are expressed by immature dendritic cells to
suppress immunostimulation of dendritic cells ; and (7) production by dendritic
cells of immunosuppressor indoleamine dioxygenase due to cytotoxic T-lymphocyte
antigen CTLA4 that interacts with costimulators T-lymphocyte activation antigens
CD80
117
and/or CD86
118
that are CTLA4 counter-receptors.
α
T
Reg
Cell Subpopulation
Two most important subsets of T
Reg
cells express forkhead box FoxP3 transcription
factor. They develop in the thymus or can be induced in peripheral sites such as
the mucosa-associated lymphoid tissue (MALT; Table
3.30
). Functional activated
human FoxP3
T
Reg
cells express a unique pattern of cell surface markers [
245
].
119
+
117
A.k.a. B7.1, BB1, CD28LG1, and LAB71.
118
A.k.a. B7.2, B70, CD28LG2, FUN1, and LAB72.
119
Markers include IL2R
α
(CD25), CD45Ro (isoform generated by CD45 transcript lacking A, B,
and C exons; i.e., low-molecular weight form [CD45
lMW
]), TNFRSF18, or glucocorticoid-induced
TNF-receptor-related
β
, glycoprotein-A repetitions predominant
(GARP; a.k.a. LRRC32), and IL1R1 and -2 (CD121a and CD121b) [
245
].
protein (GITR),
latent
TGF
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