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Title: A single early activation of invariant NK T cells confers long-term protection against collagen-induced arthritis in a ligand-specific manner
Authors: Coppieters, Ken ×
Van Beneden, Katrien
Jacques, Peggy
Dewint, Pieter
Vervloet, Ann
Vander Cruyssen, Bert
Van Calenbergh, Serge
Chen, Guangwu
Franck, Richard W
Verbruggen, Gust
Deforce, Dieter
Matthys, Patrick
Tsuji, Moriya
Rottiers, Pieter
Elewaut, Dirk #
Issue Date: Aug-2007
Publisher: American Association of Immunologists
Series Title: Journal of Immunology vol:179 issue:4 pages:2300-2309
Abstract: The glycosphingolipid alpha-galactosylceramide (alpha-GalCer) has been shown to be a potent activator of invariant NKT (iNKT) cells, rapidly inducing large amounts of both Th1 and Th2 cytokines upon injection in mice. The C-glycoside analog of alpha-GalCer (alpha-C-GalCer), by contrast, results in an enhanced Th1-type response upon activation of iNKT cells. We administered a single dose of these Ags to DBA/1 mice during the early induction phase of collagen-induced arthritis and demonstrated therapeutic efficacy of alpha-GalCer when administered early rather than late during the disease. Surprisingly, the Th1-polarizing analog alpha-C-GalCer also conferred protection. Furthermore, a biphasic role of IFN-gamma in the effect of iNKT cell stimulation was observed. Whereas in vivo neutralization of IFN-gamma release induced by either alpha-GalCer or alpha-C-GalCer early during the course of disease resulted in partial improvement of clinical arthritis symptoms, blockade of IFN-gamma release later on resulted in a more rapid onset of arthritis. Although no phenotypic changes in conventional T cells, macrophages, or APCs could be detected, important functional differences in T cell cytokine production in serum were observed upon polyclonal T cell activation, 2 wk after onset of arthritis. Whereas alpha-GalCer-treated mice produced significantly higher amounts of IL-10 upon systemic anti-CD3 stimulation compared with PBS controls, T cells from alpha-C-GalCer-treated mice, by contrast, produced substantially lower levels of cytokines, suggesting the involvement of different protective mechanisms. In conclusion, these findings suggest long-term, ligand-specific, time-dependent, and partially IFN-gamma-dependent immunomodulatory effects of iNKT cells in collagen-induced arthritis.
ISSN: 0022-1767
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Immunobiology (Rega Institute)
× corresponding author
# (joint) last author

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