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

Andrew E Hogan; Vincent O'Reilly; Margaret R Dunne; Ravindra T Dere; Shijuan G Zeng; Cashel O'Brien; Sylvie Amu; Padraic G Fallon; Mark A Exley; Cliona O'Farrelly; Xiangming Zhu; Derek G Doherty

doi:10.1016/j.clim.2011.03.016

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

Clin Immunol. 2011 Aug;140(2):196-207. doi: 10.1016/j.clim.2011.03.016. Epub 2011 Apr 13.

Authors

Andrew E Hogan¹, Vincent O'Reilly, Margaret R Dunne, Ravindra T Dere, Shijuan G Zeng, Cashel O'Brien, Sylvie Amu, Padraic G Fallon, Mark A Exley, Cliona O'Farrelly, Xiangming Zhu, Derek G Doherty

Affiliation

¹ Institute of Molecular Medicine, Trinity College Dublin, St James's Hospital, Dublin, Ireland.

PMID: 21493160
DOI: 10.1016/j.clim.2011.03.016

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigen-Presenting Cells / immunology
Antigen-Presenting Cells / metabolism
Antigens, CD1d / immunology
Cell Line
Cells, Cultured
Cytotoxicity, Immunologic / drug effects
Cytotoxicity, Immunologic / immunology
Dendritic Cells / drug effects
Dendritic Cells / immunology
Dendritic Cells / metabolism
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Galactosylceramides / chemistry
Galactosylceramides / immunology*
Galactosylceramides / pharmacology
HeLa Cells
Humans
Interferon-gamma / blood
Interferon-gamma / immunology
Interferon-gamma / metabolism
Interleukin-10 / immunology
Interleukin-10 / metabolism
Interleukin-12 / immunology
Interleukin-12 / metabolism
Interleukin-4 / blood
Interleukin-4 / immunology
Interleukin-4 / metabolism
Lymphocyte Activation / drug effects
Lymphocyte Activation / immunology*
Mice
Mice, Inbred C57BL
Molecular Structure
Natural Killer T-Cells / drug effects
Natural Killer T-Cells / immunology*
Natural Killer T-Cells / metabolism
Thiogalactosides / chemistry
Thiogalactosides / immunology*
Thiogalactosides / pharmacology
Thioglycosides / chemistry
Thioglycosides / immunology*
Thioglycosides / pharmacology

Substances

Antigens, CD1d
Galactosylceramides
Thiogalactosides
Thioglycosides
alpha-S-galactosylceramide
alpha-galactosylceramide
Interleukin-10
Interleukin-12
Interleukin-4
Interferon-gamma