NKT cell

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Natural killer T cells or NKT cells for short are a very heterogeneous subgroup of T cells . Despite their name, NKT cells are true T cells and not NK cells .

discovery

The first discovery in connection with NKT cells was made in 1986 when investigating the diversity of T cell receptors (TCR) in mice. A small population of T cells was discovered, all of which had a similar T cell receptor, which was composed of only a few of the many possible receptor gene segments. A few years later it was discovered that these cells express receptors from NK cells and that their T cell receptor does not bind to MHC molecules, but to the MHC-like molecule CD1d . CD1d presents lipids in contrast to MHC molecules which presents peptides .

These cells were called NKT cells ( NK1.1 T cells ) because, in addition to other NK receptors, they carried the lectin- like NK1.1 receptor. Today it is known, however, that not all murine NKT cells have NK1.1 (or the homolog CD161 in humans ) on their surface.

The current definition of NKT cells is therefore no longer related to NK1.1, but rather reads: NKT cells are real T cells with a restriction to CD1d.

An artificially created subtype is the cytokine-induced killer cell .

development

Like normal T cells, NKT cells develop in the thymus from precursor cells called thymocytes. In the double positive stage, i.e. H. When the molecules CD4 and CD8 are expressed on the cell surface, a certain type of T cell receptor develops in NKT cells that can recognize lipids on CD1d molecules. At this stage a positive selection takes place in which the binding of the TCR to CD1d is checked. A negative selection is not known. As they further develop in the thymus, NKT cells acquire a pre-activated status, similar to memory cells, and express receptors that are actually typical markers for NK cells, including CD56 , neural cell adhesion molecular-1 (NCAM-1) and NKG2D . Some cells also express NK1.1 (in mice) or CD161 (in humans).

function

NKT cells have a variety of functions in the body. On the one hand, they are able to destroy virus-infected cells or tumor cells through their NK cell receptors such as NKG2D. They can also eliminate infected cells by recognizing foreign lipids (e.g. from intracellular bacteria) via their T-cell receptor. In both cases, the cytotoxic effector molecules perforin and granzyme are released . Another possibility to kill infected cells is the interaction of so-called death receptors with ligands such as Fas / FasL, TRAIL or TNF / TNF receptor. The NKT cell initiates controlled cell death directly in the target cell .

In addition, NKT cells produce large amounts of cytokines such as IL-4 , IL-13 and TGF-β, but also IL-2 and IFN-γ . The effects of NKT cell activity on the immune response can be both stimulating and inhibiting, depending on which cytokines are released.

literature