International Immunology

This Article Full Text FREE Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Search for citing articles in: ISI Web of Science (86) Request Permissions Google Scholar Articles by Liou, H.-C. Articles by Liou, M.-L. Search for Related Content PubMed PubMed Citation Articles by Liou, H.-C. Articles by Liou, M.-L. Social Bookmarking          What's this?

International Immunology, Vol. 11, No. 3, 361-371, March 1999
© 1999 Japanese Society for Immunology

c-Rel is crucial for lymphocyte proliferation but dispensable for T cell effector function

Hsiou-Chi Liou, Zhuang Jin, Joseph Tumang, Sofija Andjelic, Kendall A. Smith and Mei-Ling Liou

Cornell University Medical College, Department of Medicine, Division of Immunology, LC-929, 1300 York Avenue, New York, NY 10021, USA

Correspondence to: H.-C. Liou

The TCR signals are essential for T cell activation and proliferation, primarily through the induction of cytokine and cytokine receptors. Several transcription factor families, including NF-B/Rel, have been implicated in the regulation of cytokine gene expression in T cells in response to antigen, cytokine and mitogenic stimulation. In this study, we show that the mice with a null mutation in the lymphoid-specific c-Rel gene have normal development of lymphoid tissues and T cell compartment. However, T cells derived from the c-Rel knockout mice have several functional abnormalities. The c-Rel-deficient T lymphocytes fail to respond to activation and proliferation signals mediated by the TCR and mitogens in vitro. This is attributed to an impaired production of cytokines IL-2, IL-3 and granulocyte macrophage colony stimulating factor. In addition, the induction of IL-2R chain is impaired in the c-Rel^–/– T cells. The poor expression of cytokines and IL-2R chain correlates with a reduced nuclear translocation of NF-B components in c-Rel^–/– T cells. Since activation is prerequisite for differentiation into effector cells, c-Rel^–/– T cells failed to differentiate into cytotoxic T cells or T_h cells without rescuing cytokines. However, upon supplement with exogenous IL-2, the c-Rel^–/– cytotoxic T lymphocytes are able to execute cytotoxicity and the c-Rel^–/– T_h cells are capable of providing help to normal B cells. These data suggest that c-Rel is important for inducible cytokine and cytokine receptor expression, and a key regulator of early activation and proliferation in T cells.

Keywords: c-Rel, lymphocyte, proliferation, T cell

Transmitting editor: L. H. Glimcher

CiteULike    Connotea    Del.icio.us    What's this?

This article has been cited by other articles:

				I. Castro, J. A. Wright, B. Damdinsuren, K. L. Hoek, G. Carlesso, N. P. Shinners, R. M. Gerstein, R. T. Woodland, R. Sen, and W. N. Khan B Cell Receptor-Mediated Sustained c-Rel Activation Facilitates Late Transitional B Cell Survival through Control of B Cell Activating Factor Receptor and NF-{kappa}B2 J. Immunol., June 15, 2009; 182(12): 7729 - 7737. [Abstract] [Full Text] [PDF]

				Y.-C. Lu, I. Kim, E. Lye, F. Shen, N. Suzuki, S. Suzuki, S. Gerondakis, S. Akira, S. L. Gaffen, W.-C. Yeh, et al. Differential Role for c-Rel and C/EBP{beta}/{delta} in TLR-Mediated Induction of Proinflammatory Cytokines J. Immunol., June 1, 2009; 182(11): 7212 - 7221. [Abstract] [Full Text] [PDF]

				W. Kim, Y.-Y. Fan, R. Smith, B. Patil, G. K. Jayaprakasha, D. N. McMurray, and R. S. Chapkin Dietary Curcumin and Limonin Suppress CD4+ T-Cell Proliferation and Interleukin-2 Production in Mice J. Nutr., May 1, 2009; 139(5): 1042 - 1048. [Abstract] [Full Text] [PDF]

				S. Mise-Omata, E. Kuroda, T. Sugiura, U. Yamashita, Y. Obata, and T. S. Doi The NF-{kappa}B RelA Subunit Confers Resistance to Leishmania major by Inducing Nitric Oxide Synthase 2 and Fas Expression but Not Th1 Differentiation J. Immunol., April 15, 2009; 182(8): 4910 - 4916. [Abstract] [Full Text] [PDF]

				A. Valerio, M. Dossena, P. Bertolotti, F. Boroni, I. Sarnico, G. Faraco, A. Chiarugi, A. Frontini, A. Giordano, H.-C. Liou, et al. Leptin Is Induced in the Ischemic Cerebral Cortex and Exerts Neuroprotection Through NF-{kappa}B/c-Rel-Dependent Transcription Stroke, February 1, 2009; 40(2): 610 - 617. [Abstract] [Full Text] [PDF]

				K. E. King, R. M. Ponnamperuma, C. Allen, H. Lu, P. Duggal, Z. Chen, C. Van Waes, and W. C. Weinberg The p53 Homologue {Delta}Np63{alpha} Interacts with the Nuclear Factor-{kappa}B Pathway to Modulate Epithelial Cell Growth Cancer Res., July 1, 2008; 68(13): 5122 - 5131. [Abstract] [Full Text] [PDF]

				M. Touma, V. Antonini, M. Kumar, S. L. Osborn, A. M. Bobenchik, D. B. Keskin, J. E. Connolly, M. J. Grusby, E. L. Reinherz, and L. K. Clayton Functional Role for I{kappa}BNS in T Cell Cytokine Regulation As Revealed by Targeted Gene Disruption J. Immunol., August 1, 2007; 179(3): 1681 - 1692. [Abstract] [Full Text] [PDF]

				L. S. Treml, G. Carlesso, K. L. Hoek, J. E. Stadanlick, T. Kambayashi, R. J. Bram, M. P. Cancro, and W. N. Khan TLR Stimulation Modifies BLyS Receptor Expression in Follicular and Marginal Zone B Cells J. Immunol., June 15, 2007; 178(12): 7531 - 7539. [Abstract] [Full Text] [PDF]

				R. J. Carmody, Q. Ruan, H.-C. Liou, and Y. H. Chen Essential Roles of c-Rel in TLR-Induced IL-23 p19 Gene Expression in Dendritic Cells J. Immunol., January 1, 2007; 178(1): 186 - 191. [Abstract] [Full Text] [PDF]

				A. R. Judge, A. Koncarevic, R. B. Hunter, H.-C. Liou, R. W. Jackman, and S. C. Kandarian Role for I{kappa}B{alpha}, but not c-Rel, in skeletal muscle atrophy Am J Physiol Cell Physiol, January 1, 2007; 292(1): C372 - C382. [Abstract] [Full Text] [PDF]

				I. Inta, S. Paxian, I. Maegele, W. Zhang, M. Pizzi, P. Spano, I. Sarnico, S. Muhammad, O. Herrmann, D. Inta, et al. Bim and Noxa Are Candidates to Mediate the Deleterious Effect of the NF-{kappa}B Subunit RelA in Cerebral Ischemia J. Neurosci., December 13, 2006; 26(50): 12896 - 12903. [Abstract] [Full Text] [PDF]

				K. A. Cieslik, W.-G. Deng, and K. K. Wu Essential Role of C-Rel in Nitric-Oxide Synthase-2 Transcriptional Activation: Time-Dependent Control by Salicylate Mol. Pharmacol., December 1, 2006; 70(6): 2004 - 2014. [Abstract] [Full Text] [PDF]

				C. M. Tato, N. Mason, D. Artis, S. Shapira, J. C. Caamano, J. H. Bream, H.-C. Liou, and C. A. Hunter Opposing roles of NF-{kappa}B family members in the regulation of NK cell proliferation and production of IFN-{gamma} Int. Immunol., April 1, 2006; 18(4): 505 - 513. [Abstract] [Full Text] [PDF]

				Y. Tao, D. Yan, Q. Yang, R. Zeng, and Y. Wang Low K+ Promotes NF-{kappa}B/DNA Binding in Neuronal Apoptosis Induced by K+ Loss Mol. Cell. Biol., February 1, 2006; 26(3): 1038 - 1050. [Abstract] [Full Text] [PDF]

				W. Xu and J. J. Zhang Stat1-Dependent Synergistic Activation of T-bet for IgG2a Production during Early Stage of B Cell Activation J. Immunol., December 1, 2005; 175(11): 7419 - 7424. [Abstract] [Full Text] [PDF]

				E. S. Hwang, J.-H. Hong, and L. H. Glimcher IL-2 production in developing Th1 cells is regulated by heterodimerization of RelA and T-bet and requires T-bet serine residue 508 J. Exp. Med., November 7, 2005; 202(9): 1289 - 1300. [Abstract] [Full Text] [PDF]

				R. A. Corn, C. Hunter, H.-C. Liou, U. Siebenlist, and M. R. Boothby Opposing Roles for RelB and Bcl-3 in Regulation of T-Box Expressed in T Cells, GATA-3, and Th Effector Differentiation J. Immunol., August 15, 2005; 175(4): 2102 - 2110. [Abstract] [Full Text] [PDF]

				J. M. Levenson, S. Choi, S.-Y. Lee, Y. A. Cao, H. J. Ahn, K. C. Worley, M. Pizzi, H.-C. Liou, and J. D. Sweatt A Bioinformatics Analysis of Memory Consolidation Reveals Involvement of the Transcription Factor c-Rel J. Neurosci., April 21, 2004; 24(16): 3933 - 3943. [Abstract] [Full Text] [PDF]

				N. J. Mason, H.-C. Liou, and C. A. Hunter T Cell-Intrinsic Expression of c-Rel Regulates Th1 Cell Responses Essential for Resistance to Toxoplasma gondii J. Immunol., March 15, 2004; 172(6): 3704 - 3711. [Abstract] [Full Text] [PDF]

				S. Grundstrom, P. Anderson, P. Scheipers, and A. Sundstedt Bcl-3 and NF{kappa}B p50-p50 Homodimers Act as Transcriptional Repressors in Tolerant CD4+ T Cells J. Biol. Chem., February 27, 2004; 279(9): 8460 - 8468. [Abstract] [Full Text] [PDF]

				B. M. Sullivan, A. Juedes, S. J. Szabo, M. von Herrath, and L. H. Glimcher Antigen-driven effector CD8 T cell function regulated by T-bet PNAS, December 23, 2003; 100(26): 15818 - 15823. [Abstract] [Full Text] [PDF]

				E. Chiffoleau, T. Kobayashi, M. C. Walsh, C. G. King, P. T. Walsh, W. W. Hancock, Y. Choi, and L. A. Turka TNF Receptor-Associated Factor 6 Deficiency during Hemopoiesis Induces Th2-Polarized Inflammatory Disease J. Immunol., December 1, 2003; 171(11): 5751 - 5759. [Abstract] [Full Text] [PDF]

				S.-E. Lamhamedi-Cherradi, S. Zheng, B. A. Hilliard, L. Xu, J. Sun, S. Alsheadat, H.-C. Liou, and Y. H. Chen Transcriptional Regulation of Type I Diabetes by NF-{kappa}B J. Immunol., November 1, 2003; 171(9): 4886 - 4892. [Abstract] [Full Text] [PDF]

				J. L. Smith, I. Collins, G. V. R. Chandramouli, W. G. Butscher, E. Zaitseva, W. J. Freebern, C. M. Haggerty, V. Doseeva, and K. Gardner Targeting Combinatorial Transcriptional Complex Assembly at Specific Modules within the Interleukin-2 Promoter by the Immunosuppressant SB203580 J. Biol. Chem., October 17, 2003; 278(42): 41034 - 41046. [Abstract] [Full Text] [PDF]

				T. Koike, H. Yamagishi, Y. Hatanaka, A. Fukushima, J.-w. Chang, Y. Xia, M. Fields, P. Chandler, and M. Iwashima A Novel ERK-dependent Signaling Process That Regulates Interleukin-2 Expression in a Late Phase of T Cell Activation J. Biol. Chem., April 25, 2003; 278(18): 15685 - 15692. [Abstract] [Full Text] [PDF]

				S. Rao, S. Gerondakis, D. Woltring, and M. F. Shannon c-Rel Is Required for Chromatin Remodeling Across the IL-2 Gene Promoter J. Immunol., April 1, 2003; 170(7): 3724 - 3731. [Abstract] [Full Text] [PDF]

				D. Artis, K. Speirs, K. Joyce, M. Goldschmidt, J. Caamano, C. A. Hunter, and P. Scott NF-{kappa}B1 Is Required for Optimal CD4+ Th1 Cell Development and Resistance to Leishmania major J. Immunol., February 15, 2003; 170(4): 1995 - 2003. [Abstract] [Full Text] [PDF]

				M. Vig, A. George, R. Sen, J. Durdik, S. Rath, and V. Bal Commitment of Activated T Cells to Secondary Responsiveness Is Enhanced by Signals Mediated by cAMP-Dependent Protein Kinase A-I Mol. Pharmacol., December 1, 2002; 62(6): 1471 - 1481. [Abstract] [Full Text] [PDF]

				P. W. Finn, H. He, C. Ma, T. Mueller, J. R. Stone, H.-C. Liou, M. R. Boothby, and D. L. Perkins Molecular profiling of the role of the NF-{kappa}B family of transcription factors during alloimmunity J. Leukoc. Biol., November 1, 2002; 72(5): 1054 - 1062. [Abstract] [Full Text] [PDF]

				Y.-W. He Orphan nuclear receptors in T lymphocyte development J. Leukoc. Biol., September 1, 2002; 72(3): 440 - 446. [Abstract] [Full Text] [PDF]

				C. Y. Hsia, S. Cheng, A. M. Owyang, S. F. Dowdy, and H.-C. Liou c-Rel regulation of the cell cycle in primary mouse B lymphocytes Int. Immunol., August 1, 2002; 14(8): 905 - 916. [Abstract] [Full Text] [PDF]

				J. Caamano and C. A. Hunter NF-{kappa}B Family of Transcription Factors: Central Regulators of Innate and Adaptive Immune Functions Clin. Microbiol. Rev., July 1, 2002; 15(3): 414 - 429. [Abstract] [Full Text] [PDF]

				C. M. Tato and C. A. Hunter Host-Pathogen Interactions: Subversion and Utilization of the NF-{kappa}B Pathway during Infection Infect. Immun., July 1, 2002; 70(7): 3311 - 3317. [Full Text] [PDF]

				M. Pizzi, F. Goffi, F. Boroni, M. Benarese, S. E. Perkins, H.-C. Liou, and P. Spano Opposing Roles for NF-kappa B/Rel Factors p65 and c-Rel in the Modulation of Neuron Survival Elicited by Glutamate and Interleukin-1beta J. Biol. Chem., May 31, 2002; 277(23): 20717 - 20723. [Abstract] [Full Text] [PDF]

				K. Speirs, J. Caamano, M. H. Goldschmidt, C. A. Hunter, and P. Scott NF-{kappa}B2 Is Required for Optimal CD40-Induced IL-12 Production but Dispensable for Th1 Cell Differentiation J. Immunol., May 1, 2002; 168(9): 4406 - 4413. [Abstract] [Full Text] [PDF]

				M. Iwashima, M. Takamatsu, H. Yamagishi, Y. Hatanaka, Y.-Y. Huang, C. McGinty, S. Yamasaki, and T. Koike Genetic evidence for Shc requirement in TCR-induced c-Rel nuclear translocation and IL-2 expression PNAS, April 2, 2002; 99(7): 4544 - 4549. [Abstract] [Full Text] [PDF]

				J. D. Mintern, G. Belz, S. Gerondakis, F. R. Carbone, and W. R. Heath The Cross-Priming APC Requires a Rel-Dependent Signal to Induce CTL J. Immunol., April 1, 2002; 168(7): 3283 - 3287. [Abstract] [Full Text] [PDF]

				K. J. Haley, A. Ciota, J. P. Contreras, M. R. Boothby, D. L. Perkins, and P. W. Finn Alterations in lung collectins in an adaptive allergic immune response Am J Physiol Lung Cell Mol Physiol, March 1, 2002; 282(3): L573 - L584. [Abstract] [Full Text] [PDF]

				D. S. Weih, Z. B. Yilmaz, and F. Weih Essential Role of RelB in Germinal Center and Marginal Zone Formation and Proper Expression of Homing Chemokines J. Immunol., August 15, 2001; 167(4): 1909 - 1919. [Abstract] [Full Text] [PDF]

				W. F. Tam, W. Wang, and R. Sen Cell-Specific Association and Shuttling of I{kappa}B{alpha} Provides a Mechanism for Nuclear NF-{kappa}B in B Lymphocytes Mol. Cell. Biol., July 15, 2001; 21(14): 4837 - 4846. [Abstract] [Full Text] [PDF]

				Y. Zheng, F. Ouaaz, P. Bruzzo, V. Singh, S. Gerondakis, and A. A. Beg NF-{{kappa}}B RelA (p65) Is Essential for TNF-{{alpha}}-Induced Fas Expression but Dispensable for Both TCR-Induced Expression and Activation-Induced Cell Death J. Immunol., April 15, 2001; 166(8): 4949 - 4957. [Abstract] [Full Text] [PDF]

				S. Andjelic, C. Hsia, H. Suzuki, T. Kadowaki, S. Koyasu, and H.-C. Liou Phosphatidylinositol 3-Kinase and NF-{kappa}B/Rel Are at the Divergence of CD40-Mediated Proliferation and Survival Pathways J. Immunol., October 1, 2000; 165(7): 3860 - 3867. [Abstract] [Full Text] [PDF]

				Y.-W. He, C. Beers, M. L. Deftos, E. W. Ojala, K. A. Forbush, and M. J. Bevan Down-Regulation of the Orphan Nuclear Receptor ROR{gamma}t Is Essential for T Lymphocyte Maturation J. Immunol., June 1, 2000; 164(11): 5668 - 5674. [Abstract] [Full Text] [PDF]

				C. E. Donovan, D. A. Mark, H. Z. He, H.-C. Liou, L. Kobzik, Y. Wang, G. T. De Sanctis, D. L. Perkins, and P. W. Finn NF-{kappa}B/Rel Transcription Factors: c-Rel Promotes Airway Hyperresponsiveness and Allergic Pulmonary Inflammation J. Immunol., December 15, 1999; 163(12): 6827 - 6833. [Abstract] [Full Text] [PDF]

				A. G. Martin, B. San-Antonio, and M. Fresno Regulation of Nuclear Factor kappa B Transactivation. IMPLICATION OF PHOSPHATIDYLINOSITOL 3-KINASE AND PROTEIN KINASE C zeta IN c-Rel ACTIVATION BY TUMOR NECROSIS FACTOR alpha J. Biol. Chem., May 4, 2001; 276(19): 15840 - 15849. [Abstract] [Full Text] [PDF]

				A. G. Martin and M. Fresno Tumor Necrosis Factor-alpha Activation of NF-kappa B Requires the Phosphorylation of Ser-471 in the Transactivation Domain of c-Rel J. Biol. Chem., August 4, 2000; 275(32): 24383 - 24391. [Abstract] [Full Text] [PDF]

				M. Iwashima, M. Takamatsu, H. Yamagishi, Y. Hatanaka, Y.-Y. Huang, C. McGinty, S. Yamasaki, and T. Koike Genetic evidence for Shc requirement in TCR-induced c-Rel nuclear translocation and IL-2 expression PNAS, April 2, 2002; 99(7): 4544 - 4549. [Abstract] [Full Text] [PDF]

Online ISSN 1460-2377 - Print ISSN 0953-8178

Copyright © 2009 Japanese Society for Immunology

Oxford Journals Oxford University Press

• Site Map
• Privacy Policy
• Frequently Asked Questions

Other Oxford University Press sites: Oxford University Press Oxford Journals China Oxford Journals Japan American National Biography Booksellers' Information Service Children's Fiction and Poetry Children's Reference Corporate & Special Sales Dictionaries Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks Humanities International Education Unit Law Medicine Music Online Products Oxford English Dictionary Reference Rights and Permissions Science School Books Social Sciences Very Short Introductions World's Classics