Natural killer T cell

Source: Wikipedia, the free encyclopedia.
Not to be confused with
Killer T cell
.

Natural killer T (NKT) cells are a heterogeneous group of

killer T cells
(cytotoxic T cells).

Nomenclature

The term "NK T cells" was first used in mice to define a subset of T cells that expressed the natural killer (NK) cell-associated marker NK1.1 (CD161). It is now generally accepted that the term "NKT cells" refers to

CD1d-restricted T cells, present in mice and humans, some of which coexpress a heavily biased, semi-invariant T-cell receptor and NK cell markers.[2]

Molecular characterization

NKT cells are a subset of T cells that coexpress an αβ T-cell receptor, but also express a variety of molecular markers that are typically associated with NK cells, such as

NK1.1. The best-known NKT cells differ from conventional αβ T cells in that their T-cell receptors are far more limited in diversity ('invariant' or 'type 1' NKT).[3] They and other CD1d-restricted T cells ('type 2' NKT) recognize lipids and glycolipids presented by CD1d molecules, a member of the CD1 family of antigen-presenting molecules, rather than peptide-major histocompatibility complexes (MHCs). As such, NKT cells are important in recognizing glycolipids from organisms such as Mycobacterium, which causes tuberculosis
.

NKT cells include both NK1.1+ and NK1.1−, as well as CD4+, CD4−, CD8+ and CD8− cells. Natural killer T cells can share other features with NK cells, as well, such as

CD56 expression and granzyme production.[4][5]

Invariant natural killer T (iNKT) cells express high levels of and are dependent on the transcriptional regulator

promyelocytic leukemia zinc finger for their development.[6][7]

Classification

Classification of natural killer T cells into three groups has been proposed:[2]

Type 1 NKT Type 2 NKT NKT-like
Other names classical NKT
invariant NKT (iNKT)
Vα14i NKT (mouse)
Vα24i NKT (human) 		non-classical NKT
diverse NKT 		NK1.1+ T cells
CD3+ CD56+ T cells
Restriction CD1d CD1d MHC, other?
α-GalCer
reactivity 		+ - -
T-cell-receptor repertoire Vα14-Jα18:
Vβ8.2, 7, 2 (mouse)
Vα24-Jα18:
Vβ11 (human) 		diverse diverse

Invariant NKT (iNKT) cells

See also:
Type I NKT cell

The best-known subset of CD1d-dependent NKT cells expresses an invariant T-cell receptor

(TCR) α chain. These are referred to as type I or invariant NKT cells (iNKT) cells. They are notable for their ability to respond rapidly to danger signals and pro-inflammatory cytokines. Once activated, they engage in effector functions, like NK transactivation, T cell activation and differentiation, B cell activation, dendritic cell activation and cross-presentation activity, and macrophage
activation.

iNKT cells recognize lipid antigens presented by

alpha-galactosylceramide (αGalCer), which is a synthetic form of a chemical purified from the deep sea sponge Agelas mauritianus.[9] iNKT cells develop in the thymus, and distribute to the periphery. They are most commonly found in the liver, but are also found in the thymus, spleen, peripheral blood, bone marrow and fat tissue. In comparison to mice, humans have fewer iNKT cells and have a wide variation in the amount of circulating iNKT cells.[8]

Currently, there are five major distinct iNKT cell subsets. These subset cells produce a different set of cytokines once activated. The subtypes iNKT1, iNKT2 and iNKT17 mirror

neutrophils and lymphocytes.[11] Activation occurs by engagement with their invariant TCR. iNKT cells can also be indirectly activated through cytokine signaling.[8]

While iNKT cells are not very numerous, their unique properties makes them an important regulatory cell that can influence how the immune system develops.[12] They are known to play a role in chronic inflammatory diseases like autoimmune disease, asthma and metabolic syndrome. In human autoimmune diseases, their numbers are decreased in peripheral blood. It is not clear whether this is a cause or effect of the disease. Absence of microbe exposure in early development led to increased iNKT cells and immune morbidity in a mouse model.[13]

Function

Upon activation, NKT cells are able to produce large quantities of

TNF-alpha
).

NKT cells recognize protected microbial lipid agents which are presented by CD1d-expressing antigen presenting cells. This serves as a pathway for NKT cells to fight against infections and enhance the humoral immunity. The NKT cells provide support and help to B cells which act as a microbial defense and aid in targeting for B-cell vaccines.[14]

Significance

NKT cells seem to be essential for several aspects of

cancers. NKT cells have recently been implicated in the disease progression of human asthma.[15]

The clinical potential of NKT cells lies in the rapid release of cytokines (such as IL-2, IFN-gamma, TNF-alpha, and IL-4) that promote or suppress different immune responses.

Most clinical trials with NKT cells have been performed with cytokine-induced killer cells (CIK).[16]

See also

References

  1. doi:10.1159/000090193
    .
  2. ^
    S2CID 19442375
    .
  3. PMID 33506055
    .
  4. PMID 10594688
    .
  5. S2CID 22320064
    .
  6. PMID 18660811
    .
  7. PMID 18703361
    .
  8. ^
    S2CID 205491870
    .
  9. PMID 9374463
    .
  10. PMID 26802287
    .
  11. S2CID 22580270
    .
  12. PMID 23017731
    .
  13. PMID 22442383
    .
  14. PMID 24043771
    .
  15. ^ Cromie, William J. Researchers uncover cause of asthma Archived 2006-04-05 at the Wayback Machine Harvard University Gazette, March 16, 2006.
  16. S2CID 11940173.{{cite journal}}: CS1 maint: multiple names: authors list (link
    )

External links
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