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Natural killer T (NKT) cells are a heterogeneous group of T cells that share properties of both T cells and natural killer (NK) cells. Many of these cells recognize the non-polymorphic CD1d molecule, an antigen-presenting molecule that binds self- and foreign lipids and glycolipids. They constitute only 0.2% of all peripherial blood 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, coexpressing a heavily biased, semi-invariant T cell receptor (TCR) and NK cell markers. Natural killer T (NKT) cells should not be confused with natural killer (NK) cells.
Molecular Characterization
NKT cells are a subset of T cells that co-express an αβ T cell receptor (TCR), but also express a variety of molecular markers that are typically associated with NK cells, such as NK1.1. They differ from conventional αβ T cells in that their TCRs are far more limited in diversity and in that they recognize lipids and glycolipids presented by CD1d molecules, a member of the CD1 family of antigen presenting molecules, rather than peptide-MHC complexes. NKT cells include both NK1.1+ and NK1.1-, as well as CD4+, CD4-, CD8+ and CD8- cells. Natural Killer T cells share other features with NK cells as well, such as CD16 and CD56 expression and granzyme production.
Classification
Classification of natural killer T cells into three groups has been proposed.
| 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 | + | - | - |
| TCR repetoire | Vα14-Jα18: Vβ8.2, 7, 2 (mouse) Vα24-Jα18: Vβ11 (human) | diverse | diverse |
iNKT cells
The best known subset of CD1d-dependent NKT cells expresses an invariant T cell receptor α (TCR-α) chain. These are referred to as type I or invariant NKT cells (iNKT) cells.These cells are conserved between humans and mice and are implicated in many immunological processes.
Function
Upon activation, NK T cells are able to produce large quantities of interferon-gamma, IL-4, and granulocyte-macrophage colony-stimulating factor, as well as multiple other cytokines and chemokines (such as IL-2 and TNF-alpha).
Significance
NKT cells seem to be essential for several aspects of immunity because their dysfunction or deficiency leads to a development of autoimmune diseases (such as diabetes or atherosclerosis) and cancers. NKT cells have recently been implicated in the disease progression of human asthma.
References
"Natural Killer T cell"