Abstract
Natural killer T (NKT) cells are a subset of lymphocytes that express receptors characteristic of conventional T cells together with receptors typically found on natural killer cells. A key feature of NKT cells is the expression of a semi-invariant T cell receptor that is specific for glycolipid antigens presented by the unusual major histocompatibility complex class I-like molecule CD1d. While their precise immunological functions remain unknown, NKT cells have been implicated in the regulation of adaptive immune responses, including those directed against autoantigens. These findings raise the possibility that specific stimulation of NKT cells may be exploited for therapeutic purposes. A number of laboratories have tested this hypothesis, utilizing the sea sponge-derived agent ?-galactosylceramide (?-GalCer), a specific agonist of NKT cells. Administration of ?-GalCer to mice results in potent activation of NKT cells, rapid and robust cytokine production, and activation of a variety of cells of the innate and adaptive immune systems. Most notably, repeated administration of ?-GalCer to mice favors the generation of conventional T lymphocytes producing T helper (Th) type 2 cytokines such as IL-4 and IL-10. These findings suggest that ?-GalCer can modulate inflammatory conditions that are mediated by pathogenic Th1 cells. Indeed, recent studies have demonstrated that ?-GalCer prevents the development of Type 1 diabetes in non-obese diabetic mice and central nervous system inflammation in mouse models of multiple sclerosis. Collectively, these studies provide a solid foundation for the development of NKT cell ligands as pharmacological agents for treatment of autoimmune diseases.
Keywords: natural killer t cells, cd1d molecules, glycolipids, type 1 diabetes, multiple sclerosis, experimental autoimmune encephalomyelitis, immunomodulation, immunotherapy
Current Pharmaceutical Design
Title: Natural Killer T Cells as Targets for Therapeutic Intervention in Autoimmune Diseases
Volume: 9 Issue: 3
Author(s): M. T. Wilson and L. Van. Kaer
Affiliation:
Keywords: natural killer t cells, cd1d molecules, glycolipids, type 1 diabetes, multiple sclerosis, experimental autoimmune encephalomyelitis, immunomodulation, immunotherapy
Abstract: Natural killer T (NKT) cells are a subset of lymphocytes that express receptors characteristic of conventional T cells together with receptors typically found on natural killer cells. A key feature of NKT cells is the expression of a semi-invariant T cell receptor that is specific for glycolipid antigens presented by the unusual major histocompatibility complex class I-like molecule CD1d. While their precise immunological functions remain unknown, NKT cells have been implicated in the regulation of adaptive immune responses, including those directed against autoantigens. These findings raise the possibility that specific stimulation of NKT cells may be exploited for therapeutic purposes. A number of laboratories have tested this hypothesis, utilizing the sea sponge-derived agent ?-galactosylceramide (?-GalCer), a specific agonist of NKT cells. Administration of ?-GalCer to mice results in potent activation of NKT cells, rapid and robust cytokine production, and activation of a variety of cells of the innate and adaptive immune systems. Most notably, repeated administration of ?-GalCer to mice favors the generation of conventional T lymphocytes producing T helper (Th) type 2 cytokines such as IL-4 and IL-10. These findings suggest that ?-GalCer can modulate inflammatory conditions that are mediated by pathogenic Th1 cells. Indeed, recent studies have demonstrated that ?-GalCer prevents the development of Type 1 diabetes in non-obese diabetic mice and central nervous system inflammation in mouse models of multiple sclerosis. Collectively, these studies provide a solid foundation for the development of NKT cell ligands as pharmacological agents for treatment of autoimmune diseases.
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Cite this article as:
Wilson T. M. and Kaer Van. L., Natural Killer T Cells as Targets for Therapeutic Intervention in Autoimmune Diseases, Current Pharmaceutical Design 2003; 9 (3) . https://dx.doi.org/10.2174/1381612033392080
DOI https://dx.doi.org/10.2174/1381612033392080 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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