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small room in which a monk or nun lives (同)cubicle
a device that delivers an electric current as the result of a chemical reaction (同)electric cell
a room where a prisoner is kept (同)jail cell, prison cell
(biology) the basic structural and functional unit of all organisms; they may exist as independent units of life (as in monads) or may form colonies or tissues as in higher plants and animals
any small compartment; "the cells of a honeycomb"
a small unit serving as part of or as the nucleus of a larger political movement (同)cadre
the 14th letter of the Roman alphabet (同)n

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(刑務所の)『独房』;(修道院の)小さい独居室 / (ミツバチの)みつ房,巣穴 / 小さい部屋 / 『細胞』 / 電池 / 花粉室 / (共産党などの)細胞
nitrogenの化学記号

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/09/08 10:59:38」(JST)

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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 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 approximately 0.1% of all peripheral blood T cells.^[1] Natural killer T cells should not be confused with natural killer 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). 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 complexs (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 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 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	+	-	-
T-cell-receptor 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 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. Absence of microbe exposure in early development led to increased iNKT cells and immune morbidity in a mouse model.^[7]

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.^[8]

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).^[9]

References

^ 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.
^ ^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): 231–7. doi:10.1038/nri1309. PMID 15039760.
^ 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.
^ 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.
^ 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.
^ 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.
^ Olszak et al. (2012). "Microbial Exposure During Early Life Has Persistent Effects on Natural Killer T Cell Function". Science 336 (6080): 489–93. doi:10.1126/science.1219328. PMC 3437652. PMID 22442383.
^ Cromie, William J. Researchers uncover cause of asthma Harvard University Gazette, March 16, 2006.
^ Schmeel LC, Schmeel FC, Coch C, Schmidt-Wolf IG. Cytokine-induced killer cell (CIK) in cancer immunotherapy: report of the international registry on CIK cells (IRCC). J Cancer Res Clin Oncol. 2014 Nov 8. doi:10.1007/s00432-014-1864-3. PMID 25381063.

External links

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

UpToDate Contents

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1. NK細胞欠損症候群：臨床症状および診断 nk cell deficiency syndromes clinical manifestations and diagnosis
2. ナチュラルキラー（NK）細胞大顆粒リンパ球性白血病 natural killer nk cell large granular lymphocyte leukemia
3. 再生不良性貧血：病因、臨床症状および診断 aplastic anemia pathogenesis clinical manifestations and diagnosis
4. アレルギー性接触皮膚炎の基本的機序および病態生理 basic mechanisms and pathophysiology of allergic contact dermatitis
5. 造血細胞移植後の移植片対腫瘍効果の生物学 biology of the graft versus tumor effect following hematopoietic cell transplantation

English Journal

Transport and uptake of immunogenic lipids.

Freigang S, Kain L, Teyton L.SourceThe Scripps Research Institute, Department of Immunology and Microbial Science, La Jolla, USA.
Molecular immunology.Mol Immunol.2013 Sep;55(2):179-81. doi: 10.1016/j.molimm.2012.10.016. Epub 2012 Nov 20.
An increasing number of lipid mediators have been identified as key modulators of immunity. Among these is a family of glycolipids capable of cellular uptake, loading onto the MHC-like molecule CD1d and stimulation of NKT cells. NKT cells are particularly interesting because they bridge innate and a
PMID 23174352

Diverse antigen presentation by the Group 1 CD1 molecule, CD1c.

Adams EJ.SourceDepartment of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, United States. ejadams@uchicago.edu
Molecular immunology.Mol Immunol.2013 Sep;55(2):182-5. doi: 10.1016/j.molimm.2012.10.019. Epub 2012 Nov 3.
CD1 molecules are Major Histocompatibility Complex (MHC) class I-like proteins that present diverse lipid antigens to T cells. Most of our understanding of CD1 lipid presentation and T cell recognition has come from study of the invariant Natural Killer T cell recognition of CD1d. However, in additi
PMID 23127489

Japanese Journal

皮膚疾患におけるIL-22の役割

藤田英樹
日本臨床免疫学会会誌 = Japanese journal of clinical immunology 35(3), 168-175, 2012-06-30
… IL-22はIL-10, IL-19, IL-20, IL-24, IL-26等と共にIL-10ファミリーに属するサイトカインである．IL-22はCD4陽性T細胞，NK細胞，NKT細胞等の免疫担当細胞より産生され，呼吸器，腸管，皮膚，肝臓などの上皮細胞に作用する．皮膚の表皮角化細胞においては，IL-22は抗菌ペプチドの発現を誘導し自然免疫に関与する．その一方でIL-22は角化細胞の増殖を誘導し表皮肥厚を引き起こすと同時にその終末分化を阻害しバリア機能関 …
NAID 10030832602

Structure-Activity Relationship Studies of Novel Glycosphingolipids That Stimulate Natural Killer T-Cells

TASHIRO Takuya
Bioscience, biotechnology, and biochemistry 76(6), 1055-1067, 2012-06-23
… It is a ligand making a complex with CD1d protein, and it stimulates invariant natural killer T (NKT) cells, which are one of the lineages of immunocytes. … NKT cells activated by recognition of the CD1d/KRN7000 complex with its invariant T-cell receptor (TCR) can induce both protective and regulatory immune responses. …
NAID 10030817515