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A single early activation of invariant NK T cells confers long-term protection against collagen-induced arthritis in a ligand-specific manner

Ken Coppieters UGent, Katrien Van Beneden UGent, PEGGY JACQUES UGent, Pieter Dewint UGent, Ann Vervloet UGent, BERT VANDER CRUYSSEN UGent, Serge Van Calenbergh UGent, Guangwu Chen, Richard Franck and August Verbruggen UGent, et al. (2007) JOURNAL OF IMMUNOLOGY. 179(4). p.2300-2309
abstract
The glycosphingolipid a-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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
CUTTING EDGE, RECEPTOR-DEFICIENT MICE, EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS, C-GLYCOSIDE ANALOG, ALPHA-GALACTOSYLCERAMIDE, INTERFERON-GAMMA, IFN-GAMMA, GLYCOLIPID ANTIGENS, MOUSE CD1, RHEUMATOID-ARTHRITIS
journal title
JOURNAL OF IMMUNOLOGY
J. Immunol.
volume
179
issue
4
pages
2300 - 2309
Web of Science type
Article
Web of Science id
000248959200034
JCR category
IMMUNOLOGY
JCR impact factor
6.068 (2007)
JCR rank
13/117 (2007)
JCR quartile
1 (2007)
ISSN
0022-1767
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
414185
handle
http://hdl.handle.net/1854/LU-414185
date created
2008-02-25 11:37:00
date last changed
2012-06-26 14:31:21
@article{414185,
  abstract     = {The glycosphingolipid a-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.},
  author       = {Coppieters, Ken and Van Beneden, Katrien and JACQUES, PEGGY and Dewint, Pieter and Vervloet, Ann and VANDER CRUYSSEN, BERT and Van Calenbergh, Serge and Chen, Guangwu and Franck, Richard and Verbruggen, August and Deforce, Dieter and Matthys, Patrick and Tsuji, Moriya and Rottiers, Pieter and Elewaut, Dirk},
  issn         = {0022-1767},
  journal      = {JOURNAL OF IMMUNOLOGY},
  keyword      = {CUTTING EDGE,RECEPTOR-DEFICIENT MICE,EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS,C-GLYCOSIDE ANALOG,ALPHA-GALACTOSYLCERAMIDE,INTERFERON-GAMMA,IFN-GAMMA,GLYCOLIPID ANTIGENS,MOUSE CD1,RHEUMATOID-ARTHRITIS},
  language     = {eng},
  number       = {4},
  pages        = {2300--2309},
  title        = {A single early activation of invariant NK T cells confers long-term protection against collagen-induced arthritis in a ligand-specific manner},
  volume       = {179},
  year         = {2007},
}

Chicago
Coppieters, Ken, Katrien Van Beneden, Peggy Jacques, Pieter Dewint, Ann Vervloet, BERT VANDER CRUYSSEN, Serge Van Calenbergh, et al. 2007. “A Single Early Activation of Invariant NK T Cells Confers Long-term Protection Against Collagen-induced Arthritis in a Ligand-specific Manner.” Journal of Immunology 179 (4): 2300–2309.
APA
Coppieters, K., Van Beneden, K., Jacques, P., Dewint, P., Vervloet, A., VANDER CRUYSSEN, B., Van Calenbergh, S., et al. (2007). A single early activation of invariant NK T cells confers long-term protection against collagen-induced arthritis in a ligand-specific manner. JOURNAL OF IMMUNOLOGY, 179(4), 2300–2309.
Vancouver
1.
Coppieters K, Van Beneden K, Jacques P, Dewint P, Vervloet A, VANDER CRUYSSEN B, et al. A single early activation of invariant NK T cells confers long-term protection against collagen-induced arthritis in a ligand-specific manner. JOURNAL OF IMMUNOLOGY. 2007;179(4):2300–9.
MLA
Coppieters, Ken, Katrien Van Beneden, Peggy Jacques, et al. “A Single Early Activation of Invariant NK T Cells Confers Long-term Protection Against Collagen-induced Arthritis in a Ligand-specific Manner.” JOURNAL OF IMMUNOLOGY 179.4 (2007): 2300–2309. Print.