Natural Killer T cell
Encyclopedia
Natural killer T 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 cell
s.
-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
.
s 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. 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.
-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).
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.
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.
Natural killer cell
Natural 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-polymorphic
Polymorphism (biology)
Polymorphism 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...
CD1d
CD1d receptor
CD1d 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...
molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
, an antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
-presenting molecule that binds self- and foreign lipids and glycolipids. They constitute only 0.2% of all peripheral blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
T cell
T cell
T cells or T lymphocytes 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 lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
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 receptor
CD1d 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 receptor
T cell receptor
The T cell receptor or TCR is a molecule found on the surface of T lymphocytes that is 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) cells
Natural killer cell
Natural 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 cellT cell
T cells or T lymphocytes 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 lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s that co-express an αβ T cell receptor
T cell receptor
The T cell receptor or TCR is a molecule found on the surface of T lymphocytes that is 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 CD1d
CD1d receptor
CD1d 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 CD1
CD1
For the album by Throbbing Gristle, see CD1 CD1 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 peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
-MHC complexes
Major histocompatibility complex
Major histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...
. As such, NKT cells are important in recognizing glycolipids from organisms such as mycobacterium
Mycobacterium
Mycobacterium is a genus of Actinobacteria, given its own family, the Mycobacteriaceae. The genus includes pathogens known to cause serious diseases in mammals, including tuberculosis and leprosy...
, which cause tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
. 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
CD16
CD16 is a low affinity Fc receptor.It is a cluster of differentiation found on the surface of natural killer cells, neutrophil polymorphonuclear leukocytes, monocytes and macrophages...
and CD56 expression
Gene expression
Gene 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 ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
and granzyme
Granzyme
Granzymes 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, NKT cells are able to produce large quantities of interferonInterferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
-gamma, IL-4, and granulocyte
Granulocyte
Granulocytes are a category of white blood cells characterized 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...
-macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
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 immunityImmunity (medical)
Immunity 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 atherosclerosis
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation 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.