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dc.contributor.authorO'FARRELLY, CLIONAen
dc.contributor.authorO'REILLY, VINCENTen
dc.contributor.authorDunne, Margareten
dc.contributor.authorAMU, SYLVIEen
dc.contributor.authorFALLON, PADRAICen
dc.contributor.authorDOHERTY, DEREKen
dc.contributor.authorZENG, SHIJUAN GRACEen
dc.date.accessioned2011-04-19T14:28:10Z
dc.date.available2011-04-19T14:28:10Z
dc.date.issued2011en
dc.date.submitted2011en
dc.identifier.citationHogan 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, 196-207en
dc.identifier.otherYen
dc.descriptionPUBLISHEDen
dc.description.abstractActivation 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 therapiesen
dc.description.sponsorshipThis work was supported by grants from Science Foundation Ireland (AEH, RD, SA and PGF), the Irish Health Research Board (VO?R) and the Irish Research Council for Science Engineering and Technology (MRD). MAE was supported by grants R01 DK066917 and R21 CA143748. We thank Steven Porcelli for providing the C1R and HeLa transfectant cell lines and Ann Atzberger for help with cell sorting. Thanks to Conleth Feighery, John Jackson, Jacinta Kelly, Melissa Conroy, Laura Madrigal-Estebas and Shijuan Grace Zeng for helpful discussionsen
dc.format.extent196-207en
dc.language.isoenen
dc.relation.ispartofseriesClinical Immunologyen
dc.relation.ispartofseries140en
dc.relation.ispartofseries2en
dc.rightsYen
dc.subjectImmunologyen
dc.subjectdendritic cellsen
dc.titleActivation of human invariant natural killer T cells with a thioglycoside analogue of ?-galactosylceramideen
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/ofarreclen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/dunnem12en
dc.identifier.peoplefinderurlhttp://people.tcd.ie/pfallonen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/dohertdeen
dc.identifier.rssinternalid72289en
dc.identifier.doi10.1016/j.clim.2011.03.016en
dc.subject.TCDThemeImmunology, Inflammation & Infectionen
dc.subject.TCDThemeInternational Developmenten
dc.subject.TCDTagANTICANCER DRUGSen
dc.subject.TCDTagInvariant natural killer T cellsen
dc.identifier.rssurihttp://dx.doi.org/10.1016/j.clim.2011.03.016en
dc.contributor.sponsorHealth Research Board (HRB)en
dc.contributor.sponsorIrish Research Council for Science and Engineering Technology (IRCSET)en
dc.contributor.sponsorScience Foundation Ireland (SFI)en
dc.identifier.urihttp://hdl.handle.net/2262/54938


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