|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 95 No. 10 (May 15), 2000:
pp. 3162-3167
Glucocorticoids transform CD40-triggering of dendritic cells into
an alternative activation pathway resulting in antigen-presenting cells
that secrete IL-10
Delphine Rea,
Cees van Kooten,
Krista E. van
Meijgaarden,
Tom H. M. Ottenhoff,
Cornelis J. M. Melief, and
Rienk Offringa
From the Department of Immunohematology and Blood Bank and the
Department of Nephrology, Leiden University Medical Center, Leiden, The
Netherlands.
Dendritic cell (DC) activation through CD40-CD40 ligand interactions
is a key regulatory step for the development of protective T-cell
immunity and also plays an important role in the initiation of T-cell
responses involved in autoimmune diseases and allograft rejection. In
contrast to previous reports, we show that the immunosuppressive drug
dexamethasone (DEX) redirects rather than simply blocks this DC
activation process. We found that DCs triggered through CD40 in the
presence of DEX were unable to acquire high levels of costimulatory, adhesion, and major histocompatibility complex class I and II molecules
and failed to express the maturation marker CD83, whereas antigen
uptake was not affected. Moreover, DEX strikingly modified the
CD40-activated DC cytokine secretion profile by suppressing the
production of the proinflammatory cytokine interleukin (IL)-12 and
potentiating the secretion of the anti-inflammatory cytokine IL-10.
Accordingly, DEX-exposed CD40-triggered DCs displayed a decreased
T-cell allostimulatory potential and a dramatically impaired ability to
activate cloned CD4+ T helper 1 (Th1) cells. Moreover,
interaction between Th1 cells and these DCs rendered the T cells
hyporesponsive to further antigen-specific restimulation. Collectively,
our results demonstrate that DEX profoundly modulates CD40-dependent DC
activation and suggest that the resulting alternatively activated DCs
can be exploited for suppression of unwanted T-cell responses in vivo.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S. M. Hughes, B. Amadi, M. Mwiya, H. Nkamba, A. Tomkins, and D. Goldblatt
Dendritic Cell Anergy Results from Endotoxemia in Severe Malnutrition
J. Immunol.,
August 15, 2009;
183(4):
2818 - 2826.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. S. Tait, C. L. Butts, and E. M. Sternberg
The role of glucocorticoids and progestins in inflammatory, autoimmune, and infectious disease
J. Leukoc. Biol.,
October 1, 2008;
84(4):
924 - 931.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Greenberg
Proposed immunologic models of the inflammatory myopathies and potential therapeutic implications
Neurology,
November 20, 2007;
69(21):
2008 - 2019.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Perona-Wright, S. M. Anderton, S. E. M. Howie, and D. Gray
IL-10 permits transient activation of dendritic cells to tolerize T cells and protect from central nervous system autoimmune disease
Int. Immunol.,
September 1, 2007;
19(9):
1123 - 1134.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. van Duivenvoorde, W. G. H. Han, A. M. Bakker, P. Louis-Plence, L.-M. Charbonnier, F. Apparailly, E. I. H. van der Voort, C. Jorgensen, T. W. J. Huizinga, and R. E. M. Toes
Immunomodulatory Dendritic Cells Inhibit Th1 Responses and Arthritis via Different Mechanisms
J. Immunol.,
August 1, 2007;
179(3):
1506 - 1515.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Hamdi, V. Godot, M.-C. Maillot, M. V. Prejean, N. Cohen, R. Krzysiek, F. M. Lemoine, W. Zou, and D. Emilie
Induction of antigen-specific regulatory T lymphocytes by human dendritic cells expressing the glucocorticoid-induced leucine zipper
Blood,
July 1, 2007;
110(1):
211 - 219.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. M. Hockenbery, S. Cruickshank, T. C. Rodell, T. Gooley, F. Schuening, S. Rowley, D. David, M. Brunvand, B. Berryman, S. Abhyankar, et al.
A randomized, placebo-controlled trial of oral beclomethasone dipropionate as a prednisone-sparing therapy for gastrointestinal graft-versus-host disease
Blood,
May 15, 2007;
109(10):
4557 - 4563.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Bros, F. Jahrling, A. Renzing, N. Wiechmann, N.-A. Dang, A. Sutter, R. Ross, J. Knop, S. Sudowe, and A. B. Reske-Kunz
A newly established murine immature dendritic cell line can be differentiated into a mature state, but exerts tolerogenic function upon maturation in the presence of glucocorticoid
Blood,
May 1, 2007;
109(9):
3820 - 3829.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Aeberli, M. Leech, and E. F. Morand
Macrophage migration inhibitory factor and glucocorticoid sensitivity
Rheumatology,
August 1, 2006;
45(8):
937 - 943.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Cohen, E. Mouly, H. Hamdi, M.-C. Maillot, M. Pallardy, V. Godot, F. Capel, A. Balian, S. Naveau, P. Galanaud, et al.
GILZ expression in human dendritic cells redirects their maturation and prevents antigen-specific T lymphocyte response
Blood,
March 1, 2006;
107(5):
2037 - 2044.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Stock, O. Akbari, R. H. DeKruyff, and D. T. Umetsu
Respiratory Tolerance Is Inhibited by the Administration of Corticosteroids
J. Immunol.,
December 1, 2005;
175(11):
7380 - 7387.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Freeman, M. Hewison, S. V. Hughes, K. N. Evans, D. Hardie, T. K. Means, and R. Chakraverty
Expression of 11{beta}-hydroxysteroid dehydrogenase type 1 permits regulation of glucocorticoid bioavailability by human dendritic cells
Blood,
September 15, 2005;
106(6):
2042 - 2049.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. H. Tan, P. Sagoo, C. Chan, J. B. Yates, J. Campbell, S. C. Beutelspacher, B. M. J. Foxwell, G. Lombardi, and A. J. T. George
Inhibition of NF-{kappa}B and Oxidative Pathways in Human Dendritic Cells by Antioxidative Vitamins Generates Regulatory T Cells
J. Immunol.,
June 15, 2005;
174(12):
7633 - 7644.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Verginis, H. S. Li, and G. Carayanniotis
Tolerogenic Semimature Dendritic Cells Suppress Experimental Autoimmune Thyroiditis by Activation of Thyroglobulin-Specific CD4+CD25+ T Cells
J. Immunol.,
June 1, 2005;
174(11):
7433 - 7439.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Lagaraine, C. Hoarau, V. Chabot, F. Velge-Roussel, and Y. Lebranchu
Mycophenolic acid-treated human dendritic cells have a mature migratory phenotype and inhibit allogeneic responses via direct and indirect pathways
Int. Immunol.,
April 1, 2005;
17(4):
351 - 363.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. E. Wiley, M. Cwiartka, D. Alvarez, D. C. Mackenzie, J. R. Johnson, S. Goncharova, L. Lundblad, and M. Jordana
Transient Corticosteroid Treatment Permanently Amplifies the Th2 Response in a Murine Model of Asthma
J. Immunol.,
April 15, 2004;
172(8):
4995 - 5005.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Woltman and C. van Kooten
Functional modulation of dendritic cells to suppress adaptive immune responses
J. Leukoc. Biol.,
April 1, 2003;
73(4):
428 - 441.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Sundstedt, E. J. O'Neill, K. S. Nicolson, and D. C. Wraith
Role for IL-10 in Suppression Mediated by Peptide-Induced Regulatory T Cells In Vivo
J. Immunol.,
February 1, 2003;
170(3):
1240 - 1248.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Matsue, C. Yang, K. Matsue, D. Edelbaum, M. Mummert, and A. Takashima
Contrasting Impacts of Immunosuppressive Agents (Rapamycin, FK506, Cyclosporin A, and Dexamethasone) on Bidirectional Dendritic Cell-T Cell Interaction During Antigen Presentation
J. Immunol.,
October 1, 2002;
169(7):
3555 - 3564.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. D. Edwards, S. P. Manickasingham, R. Sporri, S. S. Diebold, O. Schulz, A. Sher, T. Kaisho, S. Akira, and C. Reis e Sousa
Microbial Recognition Via Toll-Like Receptor-Dependent and -Independent Pathways Determines the Cytokine Response of Murine Dendritic Cell Subsets to CD40 Triggering
J. Immunol.,
October 1, 2002;
169(7):
3652 - 3660.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. C. Motran, F. L. Diaz, A. Gruppi, D. Slavin, B. Chatton, and J. L. Bocco
Human pregnancy-specific glycoprotein 1a (PSG1a) induces alternative activation in human and mouse monocytes and suppresses the accessory cell-dependent T cell proliferation
J. Leukoc. Biol.,
September 1, 2002;
72(3):
512 - 521.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. G.S. van Halteren, E. van Etten, E. C. de Jong, R. Bouillon, B. O. Roep, and C. Mathieu
Redirection of Human Autoreactive T-Cells Upon Interaction With Dendritic Cells Modulated by TX527, an Analog of 1,25 Dihydroxyvitamin D3
Diabetes,
July 1, 2002;
51(7):
2119 - 2125.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Masterson, C. C. Sombroek, T. D. de Gruijl, Y. M. F. Graus, H. J. J. van der Vliet, S. M. Lougheed, A. J. M. van den Eertwegh, H. M. Pinedo, and R. J. Scheper
MUTZ-3, a human cell line model for the cytokine-induced differentiation of dendritic cells from CD34+ precursors
Blood,
June 28, 2002;
100(2):
701 - 703.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Woltman, C. Massacrier, J. W. de Fijter, C. Caux, and C. van Kooten
Corticosteroids Prevent Generation of CD34+-Derived Dermal Dendritic Cells But Do Not Inhibit Langerhans Cell Development
J. Immunol.,
June 15, 2002;
168(12):
6181 - 6188.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. Companjen, L. I. v. d. Wel, L. Boon, E. P. Prens, and J. D. Laman
CD40 ligation-induced cytokine production in human skin explants is partly mediated via IL-1
Int. Immunol.,
June 1, 2002;
14(6):
669 - 676.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. J. Barrat, D. J. Cua, A. Boonstra, D. F. Richards, C. Crain, H. F. Savelkoul, R. de Waal-Malefyt, R. L. Coffman, C. M. Hawrylowicz, and A. O'Garra
In Vitro Generation of Interleukin 10-producing Regulatory CD4+ T Cells Is Induced by Immunosuppressive Drugs and Inhibited by T Helper Type 1 (Th1)- and Th2-inducing Cytokines
J. Exp. Med.,
March 4, 2002;
195(5):
603 - 616.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. D. Saemann, O. Parolini, G. A. Bohmig, P. Kelemen, P.-M. Krieger, J. Neumuller, K. Knarr, W. Kammlander, W. H. Horl, C. Diakos, et al.
Bacterial metabolite interference with maturation of human monocyte-derived dendritic cells
J. Leukoc. Biol.,
February 1, 2002;
71(2):
238 - 246.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Zelenika, E. Adams, S. Humm, L. Graca, S. Thompson, S. P. Cobbold, and H. Waldmann
Regulatory T Cells Overexpress a Subset of Th2 Gene Transcripts
J. Immunol.,
February 1, 2002;
168(3):
1069 - 1079.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Woltman, J. W. de Fijter, S. W. A. Kamerling, S. W. van der Kooij, L. C. Paul, M. R. Daha, and C. van Kooten
Rapamycin induces apoptosis in monocyte- and CD34-derived dendritic cells but not in monocytes and macrophages
Blood,
July 1, 2001;
98(1):
174 - 180.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Corinti, C. Albanesi, A. la Sala, S. Pastore, and G. Girolomoni
Regulatory Activity of Autocrine IL-10 on Dendritic Cell Functions
J. Immunol.,
April 1, 2001;
166(7):
4312 - 4318.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
