Application of NKT Cells in Immunotherapy

Invariant natural killer T (iNKT) cells are a conserved T cell sublineage and an important component of the innate immune system. The invariant T cell antigen receptor (TCR) α chain on iNKT cells interacts with glycolipid presented via CD1d on antigen-presenting cells (APCs), resulting in the production of a variety of cytokines, and thus bridging the innate and adaptive immune systems. In this review, we discuss two strategies of immune modulation that target iNKT cells using either liposomal α-galactosylceramide (α-GalCer) or α-GalCer-loaded APCs. Liposomal α- GalCer generates regulatory iNKT cells, which serve to induce regulatory T cells (Treg) and can be used to diminish immune responses as is seen in autoimmunity and allergic diseases. In contrast, α-GalCer-pulsed APCs generate stimulatory iNKT cells capable of releasing pro-inflammatory cytokines and leading to adaptive immune responses that can be used for treating malignancies. Here, we summarize the modalities used to manipulate the dual nature of iNKT cell function and their tremendous potential in treating both allergic and malignant disease.