1. Activation of human invariant natural killer T cells with a thioglycoside analogue of α-galactosylceramide.
- Author
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Hogan AE, O'Reilly V, Dunne MR, Dere RT, Zeng SG, O'Brien C, Amu S, Fallon PG, Exley MA, O'Farrelly C, Zhu X, and Doherty DG
- Subjects
- Animals, Antigen-Presenting Cells immunology, Antigen-Presenting Cells metabolism, Antigens, CD1d immunology, Cell Line, Cells, Cultured, Cytotoxicity, Immunologic drug effects, Cytotoxicity, Immunologic immunology, Dendritic Cells drug effects, Dendritic Cells immunology, Dendritic Cells metabolism, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Galactosylceramides chemistry, Galactosylceramides pharmacology, HeLa Cells, Humans, Interferon-gamma blood, Interferon-gamma immunology, Interferon-gamma metabolism, Interleukin-10 immunology, Interleukin-10 metabolism, Interleukin-12 immunology, Interleukin-12 metabolism, Interleukin-4 blood, Interleukin-4 immunology, Interleukin-4 metabolism, Lymphocyte Activation drug effects, Mice, Mice, Inbred C57BL, Molecular Structure, Natural Killer T-Cells drug effects, Natural Killer T-Cells metabolism, Thiogalactosides chemistry, Thiogalactosides pharmacology, Thioglycosides chemistry, Thioglycosides pharmacology, Galactosylceramides immunology, Lymphocyte Activation immunology, Natural Killer T-Cells immunology, Thiogalactosides immunology, Thioglycosides immunology
- Abstract
Activation of CD1d-restricted invariant NKT (iNKT) cells with the glycolipid α-galactosylceramide (α-GalCer) confers protection against disease in murine models, however, clinical trials in humans have had limited impact. We synthesized a novel thioglycoside analogue of α-GalCer, denoted α-S-GalCer, and tested its efficacy for stimulating human iNKT cells in vitro. α-S-GalCer stimulated cytokine release by iNKT cells in a CD1d-dependent manner and primed CD1d(+) target cells for lysis. α-S-GalCer-stimulated iNKT cells induced maturation of monocyte-derived dendritic cells into antigen-presenting cells that released IL-12 and small amounts of IL-10. The nature and potency of α-S-GalCer and α-GalCer in human iNKT cell activation were similar. However, in contrast to α-GalCer, α-S-GalCer did not activate murine iNKT cells in vivo. Because of its enhanced stability in biological systems, α-S-GalCer may be superior to α-GalCer as a parent compound for developing adjuvant therapies for humans., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
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