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Activation of human invariant natural killer T cells with a thioglycoside analogue of ?-galactosylceramide
O'FARRELLY, CLIONA; O'REILLY, VINCENT; Dunne, Margaret; AMU, SYLVIE; FALLON, PADRAIC; DOHERTY, DEREK; ZENG, SHIJUAN GRACE
Activation of CD1d-restricted invariant NKT (iNKT) cells with the glycolipid ?-galactosylceramide (?-GalCer) confers protection against disease in murine models, however, clinical trials in humans have had limited impact. We synthesised a novel thioglycoside analogue of ?-GalCer, denoted ?-S-GalCer, and tested its efficacy for stimulating human iNKT cells in vitro. ?-S-GalCer stimulated cytokine release by iNKT cells in a CD1d-dependent manner and primed CD1d+ target cells for lysis. ?-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 ?-S-GalCer and ?-GalCer in human iNKT cell activation were similar. However, in contrast to ?-GalCer, ?-S-GalCer did not activate murine iNKT cells in vivo. Because of its enhanced stability in biological systems, ?-S-GalCer may be superior to ?-GalCer as a parent compound for developing adjuvant therapies for humans. ?We tested if a thioglycoside analogue of ?-galactosylceramide could activate human iNKT cells ??-S-GalCer stimulated CD1d-dependent cytokine release and cytotoxicity by iNKT cells ??-S-GalCer-stimulated iNKT cells induced maturation of dendritic cells ??-S-GalCer did not activate murine iNKT cells in vivo ??-S-GalCer may be superior to ?-GalCer as a parent compound for developing adjuvant therapies
Keyword(s): Immunology; dendritic cells; Immunology, Inflammation & Infection; International Development; ANTICANCER DRUGS; Invariant natural killer T cells
Publication Date:
2011
Type: Journal article
Peer-Reviewed: Yes
Language(s): English
Institution: Trinity College Dublin
Citation(s): 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, Doherty DG, Activation of human invariant natural killer T cells with a thioglycoside analogue of ?-galactosylceramide, Clinical Immunology, 140, 2, 2011, 196-207
First Indexed: 2014-05-13 05:57:00 Last Updated: 2020-12-10 07:31:46