Natural Killer T (NKT) Cells

Natural killer T (NKT) cells are a specialized population of T cells that express a semi-invariant T cell receptor (TCR alpha beta) and surface antigens typically associated with natural killer cells. The TCR on NKT cells is unique in that it recognizes glycolipid antigens presented by the MHC I-like molecule CD1d. Most NKT cells, known as type I NKT cells, express an invariant TCR alpha chain and one of a small number of TCR beta chains. The TCRs present on type I NKT cells recognize the antigen alpha-galactosylceramide (alpha-GalCer). Within this group, distinguishable subpopulations have been identified, including CD4⁺CD8^- cells and CD4^-CD8^- cells that are present in mice and humans, and CD4^-CD8⁺ cells that are found only in humans. Less is known about a smaller population of NKT cells, known as type II NKT cells (or noninvariant NKT cells), which express a wider range of TCR alpha chains and do not recognize the alpha-GalCer antigen. NKT cells can have either protective or deleterious effects due to their abilities to produce cytokines that promote either inflammation or immune tolerance. As a result, they contribute to antibacterial and antiviral immune responses, promote tumor-related immunosurveillance or immunosuppression, and inhibit or promote the development of autoimmune diseases. Like natural killer cells, NKT cells can also induce perforin-, Fas-, and TNF-related cytotoxicity, but this is generally not thought to be their primary function.