Natural killer T （NKT） cells comprise a small, but important T cell subset and are thought to bridge the innate and adaptive immune responses. The discovery of NKT cells and extensive research on their activating li...Natural killer T （NKT） cells comprise a small, but important T cell subset and are thought to bridge the innate and adaptive immune responses. The discovery of NKT cells and extensive research on their activating ligands have paved the way for modulation of these potent immunoregulatory cells in order to improve the outcome of various clinical conditions. Efforts to modulate NKT cell effector functions have ranged from therapy for influenza to anti- tumor immunotherapy. These approaches have also led to the use of NKT cell agonists such as a-Galactosylceramide （a- GalCer） and its analogs as vaccine adjuvants, an approach that is aimed at boosting specific B and T cell responses to a vaccine candidate by concomitant activation of NKT cells. In this review we will provide a comprehensive overview of the efforts made in using a-GalCer and its analogs as vaccine adjuvants. The diverse array of vaccination strategies used, as well as the role of NKT cell activating adjuvants will be discussed, with focus on vaccines against malaria, HIV, influenza and tumor vaccines. Collectively, these studies demonstrate the efficacy of NKT cell-specific agonists as adjuvants and suggest that these compounds warrant serious consideration during the development of vaccination strategies.展开更多
Natural killer T （NKT） cells are innate-like lymphocytes that generally recognize lipid antigens and are enriched in microvascular compartments of the liver. NKT cells can be activated by self- or microbial-lipid an...Natural killer T （NKT） cells are innate-like lymphocytes that generally recognize lipid antigens and are enriched in microvascular compartments of the liver. NKT cells can be activated by self- or microbial-lipid antigens and by signaling through toll-like receptors. Following activation, NKT cells rapidly secrete pro-inflammatory or anti- inflammatory cytokines and chemokines, and thereby determine the milieu for subsequent immunity or tolerance. It is becoming clear that two different subsets of NKT cells-type I and type II--have different modes of antigen recognition and have opposing roles in inflammatory liver diseases. Here we focus mainly on the roles of both NKT cell subsets in the maintenance of immune tolerance and inflammatory diseases in liver. Furthermore, how the differential activation of type I and type II NKT cells influences other innate cells and adaptive immune cells to result in important consequences for tissue integrity is discussed. It is crucial that better reagents, including CDld tetramers, be used in clinical studies to define the roles of NKT cells in liver diseases in patients.展开更多
文摘Natural killer T （NKT） cells comprise a small, but important T cell subset and are thought to bridge the innate and adaptive immune responses. The discovery of NKT cells and extensive research on their activating ligands have paved the way for modulation of these potent immunoregulatory cells in order to improve the outcome of various clinical conditions. Efforts to modulate NKT cell effector functions have ranged from therapy for influenza to anti- tumor immunotherapy. These approaches have also led to the use of NKT cell agonists such as a-Galactosylceramide （a- GalCer） and its analogs as vaccine adjuvants, an approach that is aimed at boosting specific B and T cell responses to a vaccine candidate by concomitant activation of NKT cells. In this review we will provide a comprehensive overview of the efforts made in using a-GalCer and its analogs as vaccine adjuvants. The diverse array of vaccination strategies used, as well as the role of NKT cell activating adjuvants will be discussed, with focus on vaccines against malaria, HIV, influenza and tumor vaccines. Collectively, these studies demonstrate the efficacy of NKT cell-specific agonists as adjuvants and suggest that these compounds warrant serious consideration during the development of vaccination strategies.
文摘Natural killer T （NKT） cells are innate-like lymphocytes that generally recognize lipid antigens and are enriched in microvascular compartments of the liver. NKT cells can be activated by self- or microbial-lipid antigens and by signaling through toll-like receptors. Following activation, NKT cells rapidly secrete pro-inflammatory or anti- inflammatory cytokines and chemokines, and thereby determine the milieu for subsequent immunity or tolerance. It is becoming clear that two different subsets of NKT cells-type I and type II--have different modes of antigen recognition and have opposing roles in inflammatory liver diseases. Here we focus mainly on the roles of both NKT cell subsets in the maintenance of immune tolerance and inflammatory diseases in liver. Furthermore, how the differential activation of type I and type II NKT cells influences other innate cells and adaptive immune cells to result in important consequences for tissue integrity is discussed. It is crucial that better reagents, including CDld tetramers, be used in clinical studies to define the roles of NKT cells in liver diseases in patients.
