iNKT-cell responses to glycolipids.

Invariant natural killer T (iNKT) cells are an unusual group of T lymphocytes that recognize glycolipid antigens presented by the major histocompatibility complex class I-related protein CD1d. Because iNKT cells play a regulatory role in the immune system, they are attractive targets for immunotherapy. The marine-sponge-derived glycolipid alpha-galactosylceramide (alpha-GalCer) potently activates iNKT cells. In vivo administration of alpha-GalCer to mice or humans results in rapid and robust cytokine secretion by iNKT cells, followed by the activation of a variety of cell types of the innate and adaptive immune systems. These potent immunomodulatory activities of alpha-GalCer are being exploited for therapeutic purposes. Preclinical studies in mice have demonstrated that alpha-GalCer and related glycolipids can protect mice against a variety of diseases, including cancer, infections, and several autoimmune and inflammatory conditions. Although alpha-GalCer treatment of mice is associated with unwanted side-effects, it has been proven safe in clinical trials with cancer patients. These studies have raised significant enthusiasm for the development of effective and safe iNKT-cell-based immunotherapies for a variety of human diseases.