Peer-Reviewed Journal Details
Mandatory Fields
Hogan, AE;O'Reilly, V;Dunne, MR;Dere, RT;Zeng, SJG;O'Brien, C;Amu, S;Fallon, PG;Exley, MA;O'Farrelly, C;Zhu, XM;Doherty, DG
2011
August
Journal of Clinical Immunology
Activation of human invariant natural killer T cells with a thioglycoside analogue of alpha-galactosylceramide
Published
()
Optional Fields
MATURE DENDRITIC CELLS V(ALPHA)14 NKT CELLS FUNCTIONALLY DISTINCT CANCER-PATIENTS NOD MICE B-CELLS PHASE-I LIGAND IMMUNITY SUBSETS
140
196
207
Activation of CD1d-restricted invariant NKT (iNKT) cells with the glycolipid alpha-galactosylceramide (alpha-GalCer) confers protection against disease in murine models, however, clinical trials in humans have had limited impact. We synthesized a novel thioglycoside analogue of alpha-GalCer, denoted alpha-S-GalCer, and tested its efficacy for stimulating human iNKT cells in vitro. alpha-S-GalCer stimulated cytokine release by iNKT cells in a CD1d-dependent manner and primed CD1d(+) target cells for lysis. alpha-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 alpha-S-GalCer and alpha-GalCer in human iNKT cell activation were similar. However, in contrast to alpha-GalCer, alpha-S-GalCer did not activate murine iNKT cells in vivo. Because of its enhanced stability in biological systems, alpha-S-GalCer may be superior to alpha-GalCer as a parent compound for developing adjuvant therapies for humans. (C) 2011 Elsevier Inc. All rights reserved.
SAN DIEGO
1521-6616
10.1016/j.clim.2011.03.016
Grant Details