Biomedical Engineering Reference
In-Depth Information
3.10.4.8
Natural Killer T Lymphocytes
Natural killer T cells (NKT;
0.2% of blood T cells) constitute a group of uncon-
ventional T lymphocytes that share properties of natural killer cells. They differ from
conventional
∼
T cells because their TCRs target a limited number of molecules.
They actually express a limited T-cell receptor repertoire and recognize lipidic
rather than proteic antigens presented by the non-classical major histocompatability
complex molecule CD1d. Antigen-presenting molecule CD1d binds self and foreign
lipids and glycolipids rather than MHC-associated complexes.
Natural killer T cells express the natural killer cell marker, killer cell lectin-
like KLRb1c receptor.
129
αβ
Natural killer T cells share other features with NK cells,
R3
130
and neural cell adhesion molecule NCAM1
131
such as expression of Fc
γ
and
production of granzyme (granule enzyme).
132
During infections, NKT cells proliferate rapidly and synthesize cytokines.
Furthermore, they form long-lasting contacts with relevant antigen-presenting cells,
essentially macrophages.
Activated NKT cells produce large quantities of interferon-
, interleukin-4,
and granulocyte-macrophage colony-stimulating factor (CSF2), as well as other
cytokines and chemokines, such as IL2 and TNF
γ
. These substances are rapidly
released to promote or suppress different types of immune responses.
Natural killer T cells are classified into 3 groups. Group-
1
NKT cells include
classical, invariant (iNKT), and V
α
24i NKT cells. Group-
2
NKT cells comprises
non-classical NKT cells and other types that do not belong to group 3.
NKT-like
set is composed of KLRb1
+
(CD161c
α
+
) T cells and CD3
+
(T-cell coreceptor),
NCAM1
) T cells.
NKT cells promote interactions between dendritic cells and CD8
+
(CD56
+
+
T cells.
They operate upstream from the contact between dendritic cells and CD8
+
T cells
129
A.k.a. NK1.1 and CD161.
130
Two genes — FCGR3A and FCGR3B — encodes low-affinity receptors Fc
γ
R3a (CD16a) and
Fc
γ
R3b (CD16b).
131
Neural cell adhesion molecule (or CD56) is a marker for natural killer cells and some
T-lymphocyte types, in addition to neurons.
132
Granzymes are serine peptidases released from granules (specialized secretory lysosomes) in
natural killer cells and cytotoxic T cells to destroy virus-infected cells. In humans, 5 granzyme
types exist (A-B, H, K, M) [
262
]. These 5 isoforms are synthesized as zymogens that are
processed by cathepsin-C within granules or outside. Transfer to granules requires modifications
by mannose 6-phosphate that then allows transport through mannose 6-phosphate receptor (of
IGF2R). In addition, the granzyme-B-granulysin-perforin complex can enter a cell through the
mannose 6-phosphate receptor or other types of receptors. Inside granules, granzymes link to
serglycin, a hematopoetic chondroitin sulfate proteoglycan core protein or secretory granule
proteoglycan core protein. At the site of cell contact, granule content is released in the intracellular
medium, where granzymes are stored in vesicles. Perforin assists both transfer into and out these
vesicles. Granzyme-A and -B can also be secreted and act in the extracellular milieu, where they
can provoke target cell death. In healthy humans, granzymes can be detected in plasma (granzyme-
A: 15-35 pg/ml; granzyme-B:
≤
15 pg/ml).
Search WWH ::
Custom Search