NKT

NKT cells, or natural killer T cells, are a heterogeneous subset of T lymphocytes that share properties with natural killer (NK) cells and recognize lipid antigens presented by the CD1d molecule, a non-polymorphic MHC class I–like molecule. Most NKT cells are CD1d-restricted and respond to glycolipid antigens displayed on CD1d on antigen-presenting cells.

The best-characterized subset is invariant NKT (iNKT) cells, which in humans express an invariant T cell receptor α chain (Vα24-Jα18) paired with a limited set of β chains (commonly Vβ11). In contrast, type II, or non-invariant NKT cells, possess diverse TCRs and recognize different lipid antigens. Activation can occur through microbial lipids, such as α-galactosylceramide (α-GalCer), or through endogenous lipids produced during cellular stress.

Upon activation, NKT cells rapidly secrete a spectrum of cytokines, including IL-4, IL-13, IFN-γ, and TNF-α, enabling them to bridge innate and adaptive immunity and influence the outcome of T helper cell responses. Some NKT cells also possess cytotoxic capabilities and can directly kill CD1d-expressing target cells. NKT cells are enriched in certain tissues, notably the liver, but are present in the spleen, thymus, adipose tissue, and peripheral blood.

Physiological roles include defense against certain infections, regulation of autoimmunity, modulation of inflammation, and involvement in cancer immune surveillance. Therapeutic research has explored NKT cell–targeting strategies, such as α-GalCer–based agonists, as adjuvants or cancer immunotherapies, with mixed clinical results. Dysregulation of NKT cell activity has been associated with autoimmune, allergic, and metabolic disorders.