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    Activation of human invariant natural killer T cells with a thioglycoside analogue of α-galactosylceramide


    Hogan, Andrew and O'Reilly, Vincent P. and Dunne, Margaret R. and Dere, Ravindra T. and Zeng, Shijuan G. and O'Brien, Cashel and Amu, Sylvie and Fallon, Padraic G. and Exley, Mark A. and O'Farrelly, Cliona and Zhu, Xiangming and Doherty, Derek G. (2011) Activation of human invariant natural killer T cells with a thioglycoside analogue of α-galactosylceramide. Clinical Immunology, 140 (2). pp. 196-207. ISSN 1521-6616

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    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.

    Item Type: Article
    Keywords: NKT cells; Dendritic cells; Human; Cytokines; Glycolipids;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 10993
    Identification Number: https://doi.org/10.1016/j.clim.2011.03.016
    Depositing User: Andrew Hogan
    Date Deposited: 27 Aug 2019 14:57
    Journal or Publication Title: Clinical Immunology
    Publisher: Elsevier
    Refereed: Yes
    Funders: Science Foundation Ireland (SFI), Health Research Board (HRB), Irish Research Council for Science, Engineering and Technology (IRCSET)
    URI:

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