NKT cells can be activated by glycolipid epitopes/CD1d on APCs binding to theTCRs of the NKT cell. They can also be activated by the cytokine Interleukin-12 (IL-12) produced by dendritic cells that have themselves become activated by the pathogen-associated molecular patterns (PAMPS) of microbes binding to the toll-like receptors (TLRs) of the dendritic cell.

Once activated, the NKT cells produce large quantities of cytokines that promote both innate and adaptive immunity and may also help to regulate the immune responses. Large amounts of IFN-gamma are especially produced by activated NKT cells. IFN-gamma activates NK cells and macrophages as a part of innate immunity; it also promotes the maturation of dendritic cells so that they induce a T_h1 cell response to induce adaptive immunity.