| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Laboratoire d’Immunologie des Tumeurs,
Département d’Hématologie, Institut Paoli Calmettes, Université de la Méditerranée, Marseille, France; and
Institut National de la Santé et de la Recherche Médicale, Unité 119, Marseille, France; and
§
Departments of Immunology,
¶
Microbial and Cell Culture Science, and
||
Protein Biochemistry SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406
The TNF receptor (TNFR) family plays a central role in the development of the immune response. Here we describe the reciprocal regulation of the recently identified TNFR superfamily member herpes virus entry mediator (HVEM) (TR2) and its ligand LIGHT (TL4) on T cells following activation and the mechanism of this process. T cell activation resulted in down-regulation of HVEM and up-regulation of LIGHT, which were both more pronounced in CD8+ than CD4+ T lymphocytes. The analysis of HVEM and LIGHT mRNA showed an increase in the steady state level of both mRNAs following stimulation. LIGHT, which was present in cytoplasm of resting T cells, was induced both in cytoplasm and at the cell surface. For HVEM, activation resulted in cellular redistribution, with its disappearance from cell surface. HVEM down-regulation did not rely on de novo protein synthesis, in contrast to the partial dependence of LIGHT induction. Matrix metalloproteinase inhibitors did not modify HVEM expression, but did enhance LIGHT accumulation at the cell surface. However, HVEM down-regulation was partially blocked by a neutralizing mAb to LIGHT or an HVEM-Fc fusion protein during activation. As a model, we propose that following stimulation, membrane or secreted LIGHT binds to HVEM and induces receptor down-regulation. Degradation or release of LIGHT by matrix metalloproteinases then contributes to the return to baseline levels for both LIGHT and HVEM. These results reveal a self-regulating ligand/receptor system that contributes to T cell activation through the interaction of T cells with each other and probably with other cells of the immune system.
This article has been cited by other articles:
|
|
 |
|
  G. Xu, D. Liu, I. Okwor, Y. Wang, H. Korner, S. K. P. Kung, Y.-X. Fu, and J. E. Uzonna LIGHT Is Critical for IL-12 Production by Dendritic Cells, Optimal CD4+ Th1 Cell Response, and Resistance to Leishmania major J. Immunol., November 15, 2007; 179(10): 6901 - 6909. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Pierer, F. Brentano, J. Rethage, U. Wagner, H. Hantzschel, R. E. Gay, S. Gay, and D. Kyburz The TNF superfamily member LIGHT contributes to survival and activation of synovial fibroblasts in rheumatoid arthritis Rheumatology, July 1, 2007; 46(7): 1063 - 1070. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. E. Summers-deLuca, D. D. McCarthy, B. Cosovic, L. A. Ward, C. C. Lo, S. Scheu, K. Pfeffer, and J. L. Gommerman Expression of lymphotoxin-{alpha}{beta} on antigen-specific T cells is required for DC function J. Exp. Med., May 14, 2007; 204(5): 1071 - 1081. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J Sedgmen, W. Dawicki, J. L Gommerman, K. Pfeffer, and T. H Watts LIGHT is dispensable for CD4+ and CD8+ T cell and antibody responses to influenza A virus in mice Int. Immunol., May 1, 2006; 18(5): 797 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-K. Heo, S.-A Ju, S.-C. Lee, S.-M. Park, S.-Y. Choe, B. Kwon, B. S. Kwon, and B.-S. Kim LIGHT enhances the bactericidal activity of human monocytes and neutrophils via HVEM J. Leukoc. Biol., February 1, 2006; 79(2): 330 - 338. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. C. Cheung, I. R. Humphreys, K. G. Potter, P. S. Norris, H. M. Shumway, B. R. Tran, G. Patterson, R. Jean-Jacques, M. Yoon, P. G. Spear, et al. From The Cover: Evolutionarily divergent herpesviruses modulate T cell activation by targeting the herpesvirus entry mediator cosignaling pathway PNAS, September 13, 2005; 102(37): 13218 - 13223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Mortarini, A. Scarito, D. Nonaka, M. Zanon, I. Bersani, E. Montaldi, E. Pennacchioli, R. Patuzzo, M. Santinami, and A. Anichini Constitutive Expression and Costimulatory Function of LIGHT/TNFSF14 on Human Melanoma Cells and Melanoma-Derived Microvesicles Cancer Res., April 15, 2005; 65(8): 3428 - 3436. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Cohavy, J. Zhou, C. F. Ware, and S. R. Targan LIGHT Is Constitutively Expressed on T and NK Cells in the Human Gut and Can Be Induced by CD2-Mediated Signaling J. Immunol., January 15, 2005; 174(2): 646 - 653. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Pollara, M. Jones, M. E. Handley, M. Rajpopat, A. Kwan, R. S. Coffin, G. Foster, B. Chain, and D. R. Katz Herpes Simplex Virus Type-1-Induced Activation of Myeloid Dendritic Cells: The Roles of Virus Cell Interaction and Paracrine Type I IFN Secretion J. Immunol., September 15, 2004; 173(6): 4108 - 4119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Cohavy, J. Zhou, S. W. Granger, C. F. Ware, and S. R. Targan LIGHT Expression by Mucosal T Cells May Regulate IFN-{gamma} Expression in the Intestine J. Immunol., July 1, 2004; 173(1): 251 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Gill and J. S. Hunt Soluble Receptor (DcR3) and Cellular Inhibitor of Apoptosis-2 (cIAP-2) Protect Human Cytotrophoblast Cells Against LIGHT-Mediated Apoptosis Am. J. Pathol., July 1, 2004; 165(1): 309 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Liu, C. S. Schmidt, F. Zhao, A. J. Okragly, A. Glasebrook, N. Fox, E. Galbreath, Q. Zhang, H. Y. Song, S. Na, et al. LIGHT-deficiency impairs CD8+ T cell expansion, but not effector function Int. Immunol., July 1, 2003; 15(7): 861 - 870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wan, J. Zhang, H. Luo, G. Shi, E. Kapnik, S. Kim, P. Kanakaraj, and J. Wu A TNF Family Member LIGHT Transduces Costimulatory Signals into Human T Cells J. Immunol., December 15, 2002; 169(12): 6813 - 6821. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Gill, J. Ni, and J. S. Hunt Differential Expression of LIGHT and Its Receptors in Human Placental Villi and Amniochorion Membranes Am. J. Pathol., December 1, 2002; 161(6): 2011 - 2017. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Castellano, C. Van Lint, V. Peri, E. Veithen, Y. Morel, R. Costello, D. Olive, and Y. Collette Mechanisms Regulating Expression of the Tumor Necrosis Factor-related light Gene. ROLE OF CALCIUM-SIGNALING PATHWAY IN THE TRANSCRIPTIONAL CONTROL J. Biol. Chem., November 1, 2002; 277(45): 42841 - 42851. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Shi, H. Luo, X. Wan, T. W. Salcedo, J. Zhang, and J. Wu Mouse T cells receive costimulatory signals from LIGHT, a TNF family member Blood, October 16, 2002; 100(9): 3279 - 3286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Scheu, J. Alferink, T. Potzel, W. Barchet, U. Kalinke, and K. Pfeffer Targeted Disruption of LIGHT Causes Defects in Costimulatory T Cell Activation and Reveals Cooperation with Lymphotoxin {beta} in Mesenteric Lymph Node Genesis J. Exp. Med., June 17, 2002; 195(12): 1613 - 1624. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Tamada, J. Ni, G. Zhu, M. Fiscella, B. Teng, J. M. A. van Deursen, and L. Chen Cutting Edge: Selective Impairment of CD8+ T Cell Function in Mice Lacking the TNF Superfamily Member LIGHT J. Immunol., May 15, 2002; 168(10): 4832 - 4835. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bobik and N. Kalinina Tumor Necrosis Factor Receptor and Ligand Superfamily Family Members TNFRSF14 and LIGHT: New Players in Human Atherogenesis Arterioscler. Thromb. Vasc. Biol., December 1, 2001; 21(12): 1873 - 1875. [Full Text] [PDF]
|
|
|
|
|
|
R. B. Shaikh, S. Santee, S. W. Granger, K. Butrovich, T. Cheung, M. Kronenberg, H. Cheroutre, and C. F. Ware Constitutive Expression of LIGHT on T Cells Leads to Lymphocyte Activation, Inflammation, and Tissue Destruction J. Immunol., December 1, 2001; 167(11): 6330 - 6337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. W. Granger, K. D. Butrovich, P. Houshmand, W. R. Edwards, and C. F. Ware Genomic Characterization of LIGHT Reveals Linkage to an Immune Response Locus on Chromosome 19p13.3 and Distinct Isoforms Generated by Alternate Splicing or Proteolysis J. Immunol., November 1, 2001; 167(9): 5122 - 5128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Morel, A. Truneh, R. W. Sweet, D. Olive, and R. T. Costello The TNF Superfamily Members LIGHT and CD154 (CD40 Ligand) Costimulate Induction of Dendritic Cell Maturation and Elicit Specific CTL Activity J. Immunol., September 1, 2001; 167(5): 2479 - 2486. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
