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Critical Reviews™ in Immunology
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ISSN Imprimir: 1040-8401
ISSN En Línea: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v25.i3.20
pages 183-214

iNKT-Cell Responses to Glycolipids

Vrajesh V. Parekh
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
Michael T. Wilson
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
Luc Van Kaer
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232


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 α-galactosylceramide (α-GalCer) potently activates iNKT cells. In vivo administration of α-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 α-GalCer are being exploited for therapeutic purposes. Preclinical studies in mice have demonstrated that α-GalCer and related glycolipids can protect mice against a variety of diseases, including cancer, infections, and several autoimmune and inflammatory conditions. Although α-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.

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