Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 17 November 1995:
Vol. 270. no. 5239, pp. 1215 - 1218
DOI: 10.1126/science.270.5239.1215
Prev | Table of Contents | Next

Reports

Ligand-Induced Autoregulation of IFN- Receptor Chain Expression in T Helper Cell Subsets

Erika A. Bach (1),  Susanne J. Szabo (1),  Anand S. Dighe (1),  Avi Ashkenazi,  Michel Aguet,  Kenneth M. Murphy,  Robert D. Schreiber (2)

Interferon (IFN-) responsiveness in certain cells depends on the state of cellular differentiation or activation. Here an in vitro developmental system was used to show that IFN- produced during generation of the CD4 T helper cell type 1 (T(H)1) subset extinguishes expression of the IFN- receptor beta subunit, resulting in T(H)1 cells that are unresponsive to IFN-. This beta chain loss also occurred in IFN--treated T(H)2 cells and thus represents a specific response of CD4 T cells to IFN- rather than a T(H)1-specific differentiation event. These results define a mechanism of cellular desensitization where a cytokine down-regulates expression of a receptor subunit required primarily for signaling and not ligand binding.


E. A. Bach, S. J. Szabo, A. S. Dighe, K. M. Murphy, R. D. Schreiber, Center for Immunology and Department of Pathology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
A. Ashkenazi and M. Aguet, Department of Molecular Biology, Genentech, South San Francisco, CA 94080, USA.
(1) These authors contributed equally to this work.
(2) To whom correspondence should be addressed.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Control of T helper cell differentiation through cytokine receptor inclusion in the immunological synapse.
R. A. Maldonado, M. A. Soriano, L. C. Perdomo, K. Sigrist, D. J. Irvine, T. Decker, and L. H. Glimcher (2009)
J. Exp. Med. 206, 877-892
   Abstract »    Full Text »    PDF »
STAT4 Isoforms Differentially Regulate Th1 Cytokine Production and the Severity of Inflammatory Bowel Disease.
J. T. O'Malley, R. D. Eri, G. L. Stritesky, A. N. Mathur, H.-C. Chang, H. HogenEsch, M. Srinivasan, and M. H. Kaplan (2008)
J. Immunol. 181, 5062-5070
   Abstract »    Full Text »    PDF »
IFN-{gamma} Mediates the Death of Th1 Cells in a Paracrine Manner.
K. E. Foulds, M. J. Rotte, M. A. Paley, B. Singh, D. C. Douek, B. J. Hill, J. J. O'Shea, W. T. Watford, R. A. Seder, and C.-Y. Wu (2008)
J. Immunol. 180, 842-849
   Abstract »    Full Text »    PDF »
IFN-{gamma} Acts Directly on Activated CD4+ T Cells during Mycobacterial Infection to Promote Apoptosis by Inducing Components of the Intracellular Apoptosis Machinery and by Inducing Extracellular Proapoptotic Signals.
X. Li, K. K. McKinstry, S. L. Swain, and D. K. Dalton (2007)
J. Immunol. 179, 939-949
   Abstract »    Full Text »    PDF »
In the absence of IGF-1 signaling, IFN-{gamma} suppresses human malignant T-cell growth.
L. Conti, G. Regis, A. Longo, P. Bernabei, R. Chiarle, M. Giovarelli, and F. Novelli (2007)
Blood 109, 2496-2504
   Abstract »    Full Text »    PDF »
Expression of the p60 Autolysin Enhances NK Cell Activation and Is Required for Listeria monocytogenes Expansion in IFN-{gamma}-Responsive Mice.
J. Humann, R. Bjordahl, K. Andreasen, and L. L. Lenz (2007)
J. Immunol. 178, 2407-2414
   Abstract »    Full Text »    PDF »
Aberrant Contraction of Antigen-Specific CD4 T Cells after Infection in the Absence of Gamma Interferon or Its Receptor.
J. S. Haring and J. T. Harty (2006)
Infect. Immun. 74, 6252-6263
   Abstract »    Full Text »    PDF »
Self-Limitation of Th1-Mediated Inflammation by IFN-{gamma}..
M. Feuerer, K. Eulenburg, C. Loddenkemper, A. Hamann, and J. Huehn (2006)
J. Immunol. 176, 2857-2863
   Abstract »    Full Text »    PDF »
Dynamic Regulation of IFN-{gamma} Signaling in Antigen-Specific CD8+ T Cells Responding to Infection.
J. S. Haring, G. A. Corbin, and J. T. Harty (2005)
J. Immunol. 174, 6791-6802
   Abstract »    Full Text »    PDF »
Iron regulates T-lymphocyte sensitivity to the IFN-{gamma}/STAT1 signaling pathway in vitro and in vivo.
G. Regis, M. Bosticardo, L. Conti, S. De Angelis, D. Boselli, B. Tomaino, P. Bernabei, M. Giovarelli, and F. Novelli (2005)
Blood 105, 3214-3221
   Abstract »    Full Text »    PDF »
Interferon-{gamma} acts directly on CD8+ T cells to increase their abundance during virus infection.
J. K. Whitmire, J. T. Tan, and J. L. Whitton (2005)
J. Exp. Med. 201, 1053-1059
   Abstract »    Full Text »    PDF »
Placental Expression of Interferon-{gamma} (IFN-{gamma}) and Its Receptor IFN-{gamma}R2 Fail to Switch from Early Hypoxic to Late Normotensive Development in Preeclampsia.
S. Banerjee, A. Smallwood, J. Moorhead, A. E. Chambers, A. Papageorghiou, S. Campbell, and K. Nicolaides (2005)
J. Clin. Endocrinol. Metab. 90, 944-952
   Abstract »    Full Text »    PDF »
Characterization of a Dipeptide Motif Regulating IFN-{gamma} Receptor 2 Plasma Membrane Accumulation and IFN-{gamma} Responsiveness.
S. D. Rosenzweig, O. M. Schwartz, M. R. Brown, T. L. Leto, and S. M. Holland (2004)
J. Immunol. 173, 3991-3999
   Abstract »    Full Text »    PDF »
A Novel Mutation in IFN-{gamma} Receptor 2 with Dominant Negative Activity: Biological Consequences of Homozygous and Heterozygous States.
S. D. Rosenzweig, S. E. Dorman, G. Uzel, S. Shaw, A. Scurlock, M. R. Brown, R. H. Buckley, and S. M. Holland (2004)
J. Immunol. 173, 4000-4008
   Abstract »    Full Text »    PDF »
Interferon-{gamma}: an overview of signals, mechanisms and functions.
K. Schroder, P. J. Hertzog, T. Ravasi, and D. A. Hume (2004)
J. Leukoc. Biol. 75, 163-189
   Abstract »    Full Text »    PDF »
IGF-1 down-regulates IFN-{gamma}R2 chain surface expression and desensitizes IFN-{gamma}/STAT-1 signaling in human T lymphocytes.
P. Bernabei, M. Bosticardo, G. Losana, G. Regis, F. Di Paola, S. De Angelis, M. Giovarelli, and F. Novelli (2003)
Blood 102, 2933-2939
   Abstract »    Full Text »    PDF »
Hepatitis C Virus Core Protein Differently Regulates the JAK-STAT Signaling Pathway under Interleukin-6 and Interferon-{gamma} Stimuli.
A. Hosui, K. Ohkawa, H. Ishida, A. Sato, F. Nakanishi, K. Ueda, T. Takehara, A. Kasahara, Y. Sasaki, M. Hori, et al. (2003)
J. Biol. Chem. 278, 28562-28571
   Abstract »    Full Text »    PDF »
Inhibition of IFN-{gamma} Signaling by Glucocorticoids.
X. Hu, W.-P. Li, C. Meng, and L. B. Ivashkiv (2003)
J. Immunol. 170, 4833-4839
   Abstract »    Full Text »    PDF »
Interferon {gamma} Is Required for Activation-induced Death of T Lymphocytes.
Y. Refaeli, L. Van Parijs, S. I. Alexander, and A. K. Abbas (2002)
J. Exp. Med. 196, 999-1005
   Abstract »    Full Text »    PDF »
Inhibition of IL-6 signaling by a p38-dependent pathway occurs in the absence of new protein synthesis.
S. T. Ahmed, A. Mayer, J.-D. Ji, and L. B. Ivashkiv (2002)
J. Leukoc. Biol. 72, 154-162
   Abstract »    Full Text »    PDF »
Specific Inhibition of Interferon Signal Transduction Pathways by Adenoviral Infection.
T. D. Joseph and D. C. Look (2001)
J. Biol. Chem. 276, 47136-47142
   Abstract »    Full Text »    PDF »
Regulation of IFN-{gamma} Signaling Is Essential for the Cytotoxic Activity of CD8+ T Cells.
G. Z. Tau, S. N. Cowan, J. Weisburg, N. S. Braunstein, and P. B. Rothman2 (2001)
J. Immunol. 167, 5574-5582
   Abstract »    Full Text »    PDF »
The Role of IFN-{gamma} in the Production of Th2 Subpopulations: Implications for Variable Th2-Mediated Pathologies in Autoimmunity.
A. Wensky, M. C. Garibaldi Marcondes, and J. J. Lafaille (2001)
J. Immunol. 167, 3074-3081
   Abstract »    Full Text »    PDF »
Interferon {gamma} Stabilizes the T Helper Cell Type 1 Phenotype.
Y. Zhang, R. Apilado, J. Coleman, S. Ben-Sasson, S. Tsang, J. Hu-Li, W. E. Paul, and H. Huang (2001)
J. Exp. Med. 194, 165-172
   Abstract »    Full Text »    PDF »
Interferon resistance of cutaneous T-cell lymphoma-derived clonal T-helper 2 cells allows selective viral replication.
R. Dummer, U. Dobbeling, R. Geertsen, J. Willers, G. Burg, and J. Pavlovic (2001)
Blood 97, 523-527
   Abstract »    Full Text »    PDF »
Interferon {gamma} Signaling Alters the Function of T Helper Type 1 Cells.
G. Z. Tau, T. von der Weid, B. Lu, S. Cowan, M. Kvatyuk, A. Pernis, G. Cattoretti, N. S. Braunstein, R. L. Coffman, and P. B. Rothman (2000)
J. Exp. Med. 192, 977-986
   Abstract »    Full Text »    PDF »
Lineage commitment in the immune system: the T helper lymphocyte grows up.
L. H. Glimcher and K. M. Murphy (2000)
Genes & Dev. 14, 1693-1711
   Full Text »
Ligand-Independent Down-Regulation of IFN-{gamma} Receptor 1 Following TCR Engagement.
H. Skrenta, Y. Yang, S. Pestka, and C. G. Fathman (2000)
J. Immunol. 164, 3506-3511
   Abstract »    Full Text »    PDF »
T Helper Type 2 Cell Differentiation Occurs in the Presence of Interleukin 12 Receptor {beta}2 Chain Expression and Signaling.
R. Nishikomori, R. O. Ehrhardt, and W. Strober (2000)
J. Exp. Med. 191, 847-858
   Abstract »    Full Text »    PDF »
Cutting Edge: Differential Production of Prostaglandin D2 by Human Helper T Cell Subsets.
K. Tanaka, K. Ogawa, K. Sugamura, M. Nakamura, S. Takano, and K. Nagata (2000)
J. Immunol. 164, 2277-2280
   Abstract »    Full Text »    PDF »
Surface Expression of the IFN-{gamma}R2 Chain Is Regulated by Intracellular Trafficking in Human T Lymphocytes.
L. Rigamonti, S. Ariotti, G. Losana, R. Gradini, M. A. Russo, E. Jouanguy, J.-L. Casanova, G. Forni, and F. Novelli (2000)
J. Immunol. 164, 201-207
   Abstract »    Full Text »    PDF »
Instruction for Cytokine Expression in T Helper Lymphocytes in Relation to Proliferation and Cell Cycle Progression.
A. Richter, M. Lohning, and A. Radbruch (1999)
J. Exp. Med. 190, 1439-1450
   Abstract »    Full Text »    PDF »
Nitric Oxide Suppresses Human T Lymphocyte Proliferation Through IFN-{gamma}-Dependent and IFN-{gamma}-Independent Induction of Apoptosis.
A. Allione, P. Bernabei, M. Bosticardo, S. Ariotti, G. Forni, and F. Novelli (1999)
J. Immunol. 163, 4182-4191
   Abstract »    Full Text »    PDF »
IFN-{alpha} Activates Stat6 and Leads to the Formation of Stat2:Stat6 Complexes in B Cells.
S. Gupta, M. Jiang, and A. B. Pernis (1999)
J. Immunol. 163, 3834-3841
   Abstract »    Full Text »    PDF »
Mycobacterium avium Infection of Mouse Macrophages Inhibits IFN-{gamma} Janus Kinase-STAT Signaling and Gene Induction by Down-Regulation of the IFN-{gamma} Receptor.
S. Hussain, B. S. Zwilling, and W. P. Lafuse (1999)
J. Immunol. 163, 2041-2048
   Abstract »    Full Text »    PDF »
Interleukin-12 Induces Expression of Interferon Regulatory Factor-1 via Signal Transducer and Activator of Transcription-4 in Human T Helper Type 1 Cells.
E. M. Coccia, N. Passini, A. Battistini, C. Pini, F. Sinigaglia, and L. Rogge (1999)
J. Biol. Chem. 274, 6698-6703
   Abstract »    Full Text »    PDF »
IL-4 Selectively Inhibits IL-2-Triggered Stat5 Activation, But Not Proliferation, in Human T Cells.
A. Castro, T. K. Sengupta, D. C. Ruiz, E. Yang, and L. B. Ivashkiv (1999)
J. Immunol. 162, 1261-1269
   Abstract »    Full Text »    PDF »
IL-4 Signaling Is Regulated through the Recruitment of Phosphatases, Kinases, and SOCS Proteins to the Receptor Complex.
J. LOSMAN, X.P. CHEN, H. JIANG, P.-Y. PAN, M. KASHIWADA, C. GIALLOURAKIS, S. COWAN, K. FOLTENYI, and P. ROTHMAN (1999)
Cold Spring Harb Symp Quant Biol 64, 405-416
   Abstract »    PDF »
A Selective Defect of IFN-{gamma}- But Not of IFN-{alpha}-Induced JAK/STAT Pathway in a Subset of U937 Clones Prevents the Antiretroviral Effect of IFN-{gamma} Against HIV-1.
C. Bovolenta, A. L. Lorini, B. Mantelli, L. Camorali, F. Novelli, P. Biswas, and G. Poli (1999)
J. Immunol. 162, 323-330
   Abstract »    Full Text »    PDF »
IFN-{gamma} Is Required for IL-12 Responsiveness in Mice with Candida albicans Infection.
E. Cenci, A. Mencacci, G. Del Sero, C. Fe d'Ostiani, P. Mosci, A. Bacci, C. Montagnoli, M. Kopf, and L. Romani (1998)
J. Immunol. 161, 3543-3550
   Abstract »    Full Text »    PDF »
A Signal Transducer and Activator of Transcription (Stat)4-independent Pathway for the Development of T Helper Type 1 Cells.
M. H. Kaplan, A. L. Wurster, and M. J. Grusby (1998)
J. Exp. Med. 188, 1191-1196
   Abstract »    Full Text »    PDF »
{beta}-Galactoside-Binding Protein ({beta}GBP) Alters the Cell Cycle, Up-Regulates Expression of the {alpha}- and {beta}-Chains of the IFN-{gamma} Receptor, and Triggers IFN-{gamma}-Mediated Apoptosis of Activated Human T Lymphocytes.
A. Allione, V. Wells, G. Forni, L. Mallucci, and F. Novelli (1998)
J. Immunol. 161, 2114-2119
   Abstract »    Full Text »    PDF »
Targeted disruption of the interferon-gamma receptor 2 gene results in severe immune defects in mice.
B. Lu, C. Ebensperger, Z. Dembic, Y. Wang, M. Kvatyuk, T. Lu, R. L. Coffman, S. Pestka, and P. B. Rothman (1998)
PNAS 95, 8233-8238
   Abstract »    Full Text »    PDF »
Regulation of the Interleukin (IL)-12R {beta}2 Subunit Expression in Developing T Helper 1 (Th1) and Th2 Cells.
S. J. Szabo, A. S. Dighe, U. Gubler, and K. M. Murphy (1997)
J. Exp. Med. 185, 817-824
   Abstract »    Full Text »    PDF »
Interferon-{gamma} -Receptor Deficiency in an Infant with Fatal Bacille Calmette-Guerin Infection.
E. Jouanguy, F. Altare, S. Lamhamedi, P. Revy, J.-F. Emile, M. Newport, M. Levin, S. Blanche, E. Seboun, A. Fischer, et al. (1996)
N. Engl. J. Med. 335, 1956-1962
   Full Text »    PDF »
The Structure of the Gene for the Second Chain of the Human Interferon-gamma Receptor.
S. Rhee, C. Ebensperger, Z. Dembic, and S. Pestka (1996)
J. Biol. Chem. 271, 28947-28952
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)