Activation of human invariant natural killer T cells with a thioglycoside analogue of ?-galactosylceramide
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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, Doherty DG, Activation of human invariant natural killer T cells with a thioglycoside analogue of ?-galactosylceramide, Clinical Immunology, 140, 2, 2011, 196-207Download Item:
Activation of human invariant natural killer T cells with a thioglycoside analogue of ?-galactosylceramide.pdf (Published (author's copy) - Peer Reviewed) 290.1Kb
Abstract:
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
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Grant Number
Health Research Board (HRB)
Irish Research Council for Science and Engineering Technology (IRCSET)
Science Foundation Ireland (SFI)
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http://people.tcd.ie/ofarreclhttp://people.tcd.ie/dunnem12
http://people.tcd.ie/pfallon
http://people.tcd.ie/dohertde
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Author: O'FARRELLY, CLIONA; O'REILLY, VINCENT; Dunne, Margaret; AMU, SYLVIE; FALLON, PADRAIC; DOHERTY, DEREK; ZENG, SHIJUAN GRACE
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Clinical Immunology140
2
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Immunology, dendritic cellsSubject (TCD):
Immunology, Inflammation & Infection , International Development , ANTICANCER DRUGS , Invariant natural killer T cellsDOI:
10.1016/j.clim.2011.03.016Licences: