NKT cell
From NKcells.info
Contents |
Introduction
NKT cells are lymphocytes that display both characteristics / receptors of NK cells and T cells. They have been shown to exert strong regulatory activity in autoimmune diseases and in tumor immunity (Umetsu DT et al., 2003). NKT cells are either CD4+ or double negative (CD4-CD8-). NKT cells express a limited TCR repertoire and express an invariant V14-J281 T cell receptor in mice and a V24-J15 T cell receptor in humans, recognizing glycolipid antigens presented by CD1d. Activated NKT cells rapidly produce large quantities of IL-4 and IFN-gamma (Umetsu DT et al., 2003).
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 (Jerud, 1999).
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 PMID:15039760.
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 (Van der Vliet, 1999; Vivier, 2002).
Classification
Classification of natural killer T cells into three groups has been proposed PMID:15039760.
| 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.
Their clinical potential 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, which has earned NKT cells the moniker of the ‘double-edged sword’ of the immune system.
NKT cells and diseases
"Signalling lymphocytic activation molecule (SLAM)-associated protein"-deficiency in humans and mice blocks the development of natural killer T (NKT) cells, which is a contributory factor in X-linked lymphoproliferative disease (Nichols KE, 2005 and comment to this publication).
Katchar et al. (2005 [1]) published a significantly increased number of functional [[CD56+ T-cell]]s in the blood of patients with pulmonary sarcoidosis when compared with healthy controls.
NKT cell Activators
- Isoglobotrihexosylceramide (iGB3)
- Globotrihexosylceramide (GB3)
- alpha-Galactosylceramide (a-Gal-Cer)
- Bandeiraea simplicifolia Isolectin B4
- Ganglioside GD3.2Na
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