NKTcell

Natural killer T cells, or NKT cells, are a heterogeneous subset of lymphocytes that share properties of NK cells and T cells. In humans, NKT cells are commonly divided into invariant NKT (iNKT) cells and non-invariant or type II NKT cells. iNKT cells express a semi-invariant T-cell receptor (for example, Vα24-Jα18 paired with Vβ11) and are CD1d-restricted; type II NKT cells have more diverse TCRs and also recognize lipid antigens presented by CD1d.

CD1d presents lipid and glycolipid antigens to NKT cells. The best known iNKT cell agonist is the synthetic glycolipid alpha-galactosylceramide (α-GalCer). Activation triggers rapid production of cytokines, including IFN-γ and IL-4, and can lead to cytotoxic responses. NKT cells can influence other immune cells by cytokine signaling and by direct interactions with dendritic cells, B cells, NK cells, and macrophages.

Function and roles: NKT cells influence tumor immunity, infectious disease response, autoimmunity, and metabolic regulation. They can promote anti-tumor responses through IFN-γ production and activation of NK cells, or regulate inflammation in some contexts, particularly via IL-4 and IL-10. Type II NKT cells are often viewed as regulatory; iNKT cells can be either pro- or anti-inflammatory depending on context.

Distribution and development: NKT cells develop in the thymus and, in humans, comprise a small fraction of circulating T cells (roughly 0.1–1%). They are enriched in the liver and adipose tissue and can be detected by CD1d tetramer staining loaded with α-GalCer. In mice, NK1.1 is used as a surface marker, though this varies by strain. Understanding of NKT cells continues to grow with implications for immunotherapy and vaccination.