|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 93 No. 5 (March 1), 1999:
pp. 1448-1455
Downregulation of Interleukin-12 (IL-12) Responsiveness in Human T
Cells by Transforming Growth Factor- : Relationship
With IL-12 Signaling
Cécile Pardoux,
Xiaojing Ma,
Stéphanie Gobert,
Sandra Pellegrini,
Patrick Mayeux,
Françoise Gay,
Giorgio Trinchieri, and
Salem Chouaib
From the Laboratoire Cytokines et Immunologie des Tumeurs Humaines,
INSERM U487, Institut Gustave Roussy, Villejuif; INSERM U363,
Hôpital Cochin, Paris; INSERM U276, Institut Pasteur, Paris,
France; and The Wistar Institute, Philadelphia, PA.
Interleukin-12 (IL-12) is a cytokine that plays a central role in
the control of cell-mediated immunity. We have previously shown that
transforming growth factor- 1 (TGF-) inhibitory effects on human
primary allogeneic cytotoxicity and proliferative responses interfere
with IL-12 pathway. The present study was undertaken to further
elucidate the biochemical basis of the functional interaction between
these two cytokines and to define the site of TGF- action on the
signaling pathway activated by IL-12. Our data indicate that TGF-
induced an inhibition of interferon- (IFN-) production without
affecting the IL-12R1 and IL-12R2 subunits mRNA expression by
activated T cells. We further show that TGF- has a significant inhibitory effect on the early signal transduction events following interaction of IL-12 with its receptor on activated T cells, resulting in the inhibition of both JAK2 and Tyk2 phosphorylation. In addition, TGF- was found to significantly inhibit IL-12-induced
phosphorylation of the STAT4 transcription factor. Electrophoretic
mobility shift assay indicated that TGF- induced a decrease in
IL-12-induced STAT4 DNA binding activity in T lymphocytes. This study
suggests that TGF- influences IL-12 responsiveness at least in part
by inhibiting early signaling events essential to gene induction in
IL-12-activated T cells.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M.-L. Cheng, H.-W. Chen, J.-P. Tsai, Y.-P. Lee, Y.-C. Shih, C.-M. Chang, and C.-C. Ting
Clonal restriction of the expansion of antigen-specific CD8+ memory T cells by transforming growth factor-{beta}
J. Leukoc. Biol.,
May 1, 2006;
79(5):
1033 - 1042.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. J. Schiffrin, M. E. Yousfi, M. Faure, L. Combaret, A. Donnet, S. Blum, C. Obled, and D. Breuille
Milk Casein-Based Diet Containing TGF-{beta} Controls the Inflammatory Reaction in the HLA-B27 Transgenic Rat Model
JPEN J Parenter Enteral Nutr,
July 1, 2005;
29(4_suppl):
S141 - S150.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-J. Kim, T. M. Stringfield, Y. Chen, and H. E. Broxmeyer
Modulation of cord blood CD8+ T-cell effector differentiation by TGF-{beta}1 and 4-1BB costimulation
Blood,
January 1, 2005;
105(1):
274 - 281.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Xu, P. B. Silver, T. K. Tarrant, C.-C. Chan, and R. R. Caspi
TGF-{beta} Inhibits Activation and Uveitogenicity of Primary but Not of Fully Polarized Retinal Antigen-Specific Memory-Effector T Cells
Invest. Ophthalmol. Vis. Sci.,
November 1, 2003;
44(11):
4805 - 4812.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Schroder, C. Meisel, K. Buhl, N. Profanter, N. Sievert, H.-D. Volk, and G. Grutz
Different Modes of IL-10 and TGF-{beta} to Inhibit Cytokine-Dependent IFN-{gamma} Production: Consequences for Reversal of Lipopolysaccharide Desensitization
J. Immunol.,
May 15, 2003;
170(10):
5260 - 5267.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Dennler, M.-J. Goumans, and P. ten Dijke
Transforming growth factor {beta} signal transduction
J. Leukoc. Biol.,
May 1, 2002;
71(5):
731 - 740.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. Bollard, C. Rossig, M. J. Calonge, M. H. Huls, H.-J. Wagner, J. Massague, M. K. Brenner, H. E. Heslop, and C. M. Rooney
Adapting a transforming growth factor beta -related tumor protection strategy to enhance antitumor immunity
Blood,
May 1, 2002;
99(9):
3179 - 3187.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Qadir, A. Metwali, A. M. Blum, J. Li, D. E. Elliott, and J. V. Weinstock
TGF-beta and IL-10 regulation of IFN-gamma produced in Th2-type schistosome granulomas requires IL-12
Am J Physiol Gastrointest Liver Physiol,
October 1, 2001;
281(4):
G940 - G946.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Latour, H. Tanaka, C. Demeure, V. Mateo, M. Rubio, E. J. Brown, C. Maliszewski, F. P. Lindberg, A. Oldenborg, A. Ullrich, et al.
Bidirectional Negative Regulation of Human T and Dendritic Cells by CD47 and Its Cognate Receptor Signal-Regulator Protein-{alpha}: Down-Regulation of IL-12 Responsiveness and Inhibition of Dendritic Cell Activation
J. Immunol.,
September 1, 2001;
167(5):
2547 - 2554.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Xu, K. Sumita, C. Feng, X. Xiong, H. Shen, S. Maruyama, M. Kanoh, and Y. Asano
Down-Regulation of IL-12 p40 Gene in Plasmodium berghei-Infected Mice
J. Immunol.,
July 1, 2001;
167(1):
235 - 241.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. A. Lafleur, S.-F. Jia, L. L. Worth, Z. Zhou, L. B. Owen-Schaub, and E. S. Kleinerman
Interleukin (IL)-12 and IL-12 Gene Transfer Up-Regulate Fas Expression in Human Osteosarcoma and Breast Cancer Cells
Cancer Res.,
May 1, 2001;
61(10):
4066 - 4071.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
C. Menetrier-Caux, M. C. Thomachot, L. Alberti, G. Montmain, and J. Y. Blay
IL-4 Prevents the Blockade of Dendritic Cell Differentiation Induced by Tumor Cells
Cancer Res.,
April 1, 2001;
61(7):
3096 - 3104.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
A. J. Wagers and G. S. Kansas
Potent Induction of {alpha}(1,3)-Fucosyltransferase VII in Activated CD4+ T Cells by TGF-{beta}1 Through a p38 Mitogen-Activated Protein Kinase-Dependent Pathway
J. Immunol.,
November 1, 2000;
165(9):
5011 - 5016.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.-N. Avice, M. Rubio, M. Sergerie, G. Delespesse, and M. Sarfati
CD47 Ligation Selectively Inhibits the Development of Human Naive T Cells into Th1 Effectors
J. Immunol.,
October 15, 2000;
165(8):
4624 - 4631.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Poszepczynska, M. Bagot, H. Echchakir, D. Martinvalet, M. Ramez, D. Charue, L. Boumsell, and A. Bensussan
Functional characterization of an IL-7-dependent CD4+CD8alpha alpha + Th3-type malignant cell line derived from a patient with a cutaneous T-cell lymphoma
Blood,
August 1, 2000;
96(3):
1056 - 1063.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Wang, M. Chen, K. P. Wandinger, G. Williams, and S. Dhib-Jalbut
IFN-{beta}-1b Inhibits IL-12 Production in Peripheral Blood Mononuclear Cells in an IL-10-Dependent Mechanism: Relevance to IFN-{beta}-1b Therapeutic Effects in Multiple Sclerosis
J. Immunol.,
July 1, 2000;
165(1):
548 - 557.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. A. Bickerstaff, D. Xia, R. P. Pelletier, and C. G. Orosz
Mechanisms of Graft Acceptance: Evidence That Plasminogen Activator Controls Donor-Reactive Delayed-Type Hypersensitivity Responses in Cardiac Allograft Acceptor Mice
J. Immunol.,
May 15, 2000;
164(10):
5132 - 5139.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Cipriani, G. Borsellino, F. Poccia, R. Placido, D. Tramonti, S. Bach, L. Battistini, and C. F. Brosnan
Activation of C-C beta -chemokines in human peripheral blood gamma delta T cells by isopentenyl pyrophosphate and regulation by cytokines
Blood,
January 1, 2000;
95(1):
39 - 47.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.G. Begley and N.A. Nicola
Resolving Conflicting Signals: Cross Inhibition of Cytokine Signaling Pathways
Blood,
March 1, 1999;
93(5):
1443 - 1447.
[Full Text]
[PDF]
|
|
|
|
|
