Natural Killer T cell

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 peripheral blood T cells.^[1]

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.^[2] 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. As such, NKT cells are important in recognizing glycolipids from organisms such as mycobacterium, which cause tuberculosis. 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.^[3][4] Invariant Natural Killer T (iNKT) cells express high levels of and are dependent on the transcriptional regulator promyelocytic leukemia zinc finger (PLZF) for their development.^[5][6]

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	+	-	-
TCR repertoire	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, NKT 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, Interleukin-13, Interleukin-17, Interleukin-21 and TNF-alpha).

Significance

NKT cells seem to be essential for several aspects of immunity because their dysfunction or deficiency has been shown to lead to the development of autoimmune diseases (such as diabetes or atherosclerosis) and cancers. NKT cells have recently been implicated in the disease progression of human asthma.^[7]

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.

References

1. ^ Jerud, ES; Bricard G, Porcelli SA (2006). "Natural Killer T cells: Roles in Tumor Immunosurveillance and Tolerance". Transfus. Med. Hemother. 33 (1): 18–36. doi:10.1159/000090193. 
2. ^ ^{a b} Godfrey, DI; MacDonald HR, Kronenberg M, Smyth MJ, Van Kaer L (2004). "NKT cells: what’s in a name?". Nat. Rev. Immunol. 4 (3): 231. doi:10.1038/nri1309. PMID 15039760. 
3. ^ Van der Vliet, HJ; Nishi N, Koezuka Y, Peyrat MA, Von Blomberg BM, Van den Eertwegh AJ, Pinedo HM, Giaccone G, Scheper RJ (1999). "Effects of alphagalactosylceramide (KRN7000), interleukin-12 and interleukin-7 on phenotype and cytokine profile of human Va24⁺ Vb11⁺ T cells". Immunology 98 (4): 557–563. doi:10.1046/j.1365-2567.1999.00920.x. PMC 2326955. PMID 10594688. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2326955. 
4. ^ Vivier, E; Anfossi N (2004). "Inhibitory NK-cell receptors on T cells. Witness of the past, actors of the future.". Nat Rev Immunol 4 (3): 190–198. doi:10.1038/nri1306. PMID 15039756. 
5. ^ Kovalovsky D, Uche OU, et al. (Sep 2008). "The BTB-zinc finger transcriptional regulator PLZF controls the development of invariant natural killer T cell effector functions.". Nature Immunology 9 (9): 1055–64. doi:10.1038/ni.1641. PMC 2662733. PMID 18660811. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2662733. 
6. ^ Savage AK, Constantinides MG, et al. (Sep 2008). "The transcription factor PLZF directs the effector program of the NKT cell lineage.". Immunity 29 (3): 391–403. doi:10.1016/j.immuni.2008.07.011. PMC 2613001. PMID 18703361. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2613001. 
7. ^ Cromie, William J. Researchers uncover cause of asthma Harvard University Gazette, March 16, 2006.

External links

• NKT cell Journal Screening
• Nature glossary on murine NKT cells
• Nature Reviews Web Focus on regulatory lymphocytes