Natural killer T (NKT) cells are a heterogeneous group of T cells that share properties of both T cells and
natural killer (NK) cellsNatural killer cells are a type of cytotoxic lymphocyte that constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses...
. Many of these cells recognize the
non-polymorphicPolymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...
CD1dCD1d is a member of the CD1 family of glycoproteins expressed on the surface of various human antigen-presenting cells. They are related to the class I MHC molecules, and are involved in the presentation of lipid antigens to T cells...
moleculeA molecule is defined as an electrically neutral group of at least two atoms in a definite arrangement held together by very strong chemical bonds. Molecules are distinguished from polyatomic ions in this strict sense...
, an
antigenAn antigen is a substance that prompts the generation of antibodies and can cause an immune response. "Self" antigens are usually tolerated by the immune system; whereas "Non-self" antigens are identified as intruders and attacked by the immune system...
-presenting molecule that binds self- and foreign lipids and glycolipids. They constitute only 0.2% of all peripheral
bloodBlood is a specialized bodily fluid that delivers necessary substances to the body's cells — such as nutrients and oxygen — and transports waste products away from those same cells....
T cell'T cells' belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocyte types, such as B cells and natural killer cells by the presence of a special receptor on their cell surface called T cell receptors...
s.
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
CD1dCD1d is a member of the CD1 family of glycoproteins expressed on the surface of various human antigen-presenting cells. They are related to the class I MHC molecules, and are involved in the presentation of lipid antigens to T cells...
-restricted T cells, present in mice and humans, coexpressing a heavily biased, semi-invariant
T cell receptorThe T cell receptor or TCR is a molecule found on the surface of T lymphocytes that is, in general, responsible for recognizing antigens bound to major histocompatibility complex molecules....
(TCR) and NK cell markers.
Natural killer T (NKT) cells should not be confused with
natural killer (NK) cellsNatural killer cells are a type of cytotoxic lymphocyte that constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses...
.
Molecular characterization
NKT cells are a subset of
T cell'T cells' belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocyte types, such as B cells and natural killer cells by the presence of a special receptor on their cell surface called T cell receptors...
s that co-express an αβ
T cell receptorThe T cell receptor or TCR is a molecule found on the surface of T lymphocytes that is, in general, responsible for recognizing antigens bound to major histocompatibility complex molecules....
(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
CD1dCD1d is a member of the CD1 family of glycoproteins expressed on the surface of various human antigen-presenting cells. They are related to the class I MHC molecules, and are involved in the presentation of lipid antigens to T cells...
molecules, a member of the
CD1CD1 is a family of glycoproteins expressed on the surface of various human antigen-presenting cells. They are related to the class I MHC molecules, and are involved in the presentation of lipid antigens to T cells...
family of antigen presenting molecules, rather than
peptidePeptides are short polymers formed from the linking, in a defined order, of α-amino acids. The link between one amino acid residue and the next is called an amide bond or a peptide bond....
-
MHC complexesThe major histocompatibility complex is a large genomic region or gene family found in most vertebrates. It is the most gene-dense region of the mammalian genome and plays an important role in the immune system and autoimmunity. The diversity of MHC is important in the immune diversity in the...
. 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
CD16CD16 is an Fc receptor.It is a cluster of differentiation found on the surface of natural killer cells, neutrophil polymorphonuclear leukocytes, monocytes and macrophages...
and CD56
expressionGene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as rRNA genes or tRNA genes, the product is a functional RNA...
and
granzymeGranzymes are serine proteases that are released by cytoplasmic granules within cytotoxic T cells and natural killer cells. Their purpose is to induce apoptosis within virus-infected cells, thus destroying them....
production. 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.
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 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, NK T cells are able to produce large quantities of
interferonInterferons are natural cell-signaling proteins produced by the cells of the immune system of most vertebrates in response to challenges such as viruses, parasites and tumor cells. They belong to the large class of glycoproteins known as cytokines and are produced by a wide variety of cells in...
-gamma, IL-4, and
granulocyteGranulocytes are a category of white blood cells characterised by the presence of granules in their cytoplasm. They are also called polymorphonuclear leukocytes because of the varying shapes of the nucleus, which is usually lobed into three segments...
-
macrophageMacrophages are white blood cells within tissues, produced by the division of monocytes. Human macrophages are about in diameter...
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
immunityImmunity is a biological term that describes a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion. Immunity involves both specific and non-specific components. The non-specific components act either as barriers or as eliminators of wide...
because their dysfunction or deficiency has been shown to lead to the development of autoimmune diseases (such as diabetes or
atherosclerosisAtherosclerosis is the condition in which an artery wall thickens as the result of a build-up of fatty materials such as cholesterol...
) and cancers. NKT cells have recently been implicated in the disease progression of human asthma.
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.
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