J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/01/81/10 $2.00
Volume 185 January 1997 81-90

Membrane Tumor Necrosis Factor (TNF) Induced Cooperative Signaling of TNFR60 and TNFR80 Favors Induction of Cell Death Rather Than Virus Production in HIV-infected T Cells

By Janis K. Lazdins,^* Matthias Grell, Maja R. Walker,^* Kathie Woods-Cook,^* Peter Scheurich, and Klaus Pfizenmaier

From the ^* Division Pharma, Ciba, 4002 Basel, Switzerland; and  Institute of Cell Biology and Immunology, University of Stuttgart, 70569 Stuttgart, Germany

Tumor necrosis factor (TNF) and lymphotoxin (LT) are highly pleiotropic cytokines that play a central role in regulating HIV-1 replication. These cytokines express their activities through two membrane receptors, TNFR60 (p55-60) and TNFR80 (p75-80). In the present study we have demonstrated by means of antagonistic and agonistic receptor-specific antibodies that in latently infected lymphocytic (ACH-2) cells the TNFR60 plays a dominant role in signaling HIV production, although selective activation of TNFR80 by receptor-specific antibodies can also induce HIV production. Unexpectedly, when both TNFRs were activated simultaneously by agonistic antibodies or coculture with cells expressing a noncleavable membrane form of TNF, HIV production was downregulated and induction of cell death was enhanced in ACH-2 cells. More relevant, in vitro HIV-infected peripheral blood lymphocytes cocultured with cells expressing membrane TNF underwent rapid induction of apoptosis with a subsequent reduced HIV production of these lymphocytes cultures. This was not observed with HIV-infected lymphocytes treated with soluble TNF. These data provide evidence for the differential trigger potential of membrane versus soluble TNF and show that TNFR80 is an important modulator of TNF responsiveness of HIV-infected T cells via cooperative signaling with TNFR60.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Quaranta, M. G., Napolitano, A., Sanchez, M., Giordani, L., Mattioli, B., Viora, M. (2007). HIV-1 Nef impairs the dynamic of DC/NK crosstalk: different outcome of CD56dim and CD56bright NK cell subsets. FASEB J. 21: 2323-2334 [Abstract] [Full Text]  
• Mezyk-Kopec, R., Bzowska, M., Potempa, J., Bzowska, M., Jura, N., Sroka, A., Black, R. A., Bereta, J. (2005). Inactivation of Membrane Tumor Necrosis Factor Alpha by Gingipains from Porphyromonas gingivalis. Infect. Immun. 73: 1506-1514 [Abstract] [Full Text]  
• Andrade, R. M., Wessendarp, M., Subauste, C. S. (2003). CD154 Activates Macrophage Antimicrobial Activity in the Absence of IFN-{gamma} through a TNF-{alpha}-Dependent Mechanism. J. Immunol. 171: 6750-6756 [Abstract] [Full Text]  
• Trabattoni, D., Lo Caputo, S., Biasin, M., Seminari, E., Di Pietro, M., Ravasi, G., Mazzotta, F., Maserati, R., Clerici, M. (2002). Modulation of Human Immunodeficiency Virus (HIV)-Specific Immune Response by Using Efavirenz, Nelfinavir, and Stavudine in a Rescue Therapy Regimen for HIV-Infected, Drug-Experienced Patients. CVI 9: 1114-1118 [Abstract] [Full Text]  
• Lenardo, M. J., Angleman, S. B., Bounkeua, V., Dimas, J., Duvall, M. G., Graubard, M. B., Hornung, F., Selkirk, M. C., Speirs, C. K., Trageser, C., Orenstein, J. O., Bolton, D. L. (2002). Cytopathic Killing of Peripheral Blood CD4+ T Lymphocytes by Human Immunodeficiency Virus Type 1 Appears Necrotic rather than Apoptotic and Does Not Require env. J. Virol. 76: 5082-5093 [Abstract] [Full Text]  
• Neely, G. G., Robbins, S. M., Amankwah, E. K., Epelman, S., Wong, H., Spurrell, J. C. L., Jandu, K. K., Zhu, W., Fogg, D. K., Brown, C. B., Mody, C. H. (2001). Lipopolysaccharide-Stimulated or Granulocyte-Macrophage Colony-Stimulating Factor-Stimulated Monocytes Rapidly Express Biologically Active IL-15 on Their Cell Surface Independent of New Protein Synthesis. J. Immunol. 167: 5011-5017 [Abstract] [Full Text]  
• Lawn, S. D., Butera, S. T., Folks, T. M. (2001). Contribution of Immune Activation to the Pathogenesis and Transmission of Human Immunodeficiency Virus Type 1 Infection. Clin. Microbiol. Rev. 14: 753-777 [Abstract] [Full Text]  
• Elzey, B. D., Griffith, T. S., Herndon, J. M., Barreiro, R., Tschopp, J., Ferguson, T. A. (2001). Regulation of Fas Ligand-Induced Apoptosis by TNF. J. Immunol. 167: 3049-3056 [Abstract] [Full Text]  
• Baseta, J. G., Stutman, O. (2000). TNF Regulates Thymocyte Production by Apoptosis and Proliferation of the Triple Negative (CD3-CD4-CD8-) Subset. J. Immunol. 165: 5621-5630 [Abstract] [Full Text]  
• ATEN, J., ROOS, A., CLAESSEN, N., SCHILDER-TOL, E. J. M., TEN BERGE, I. J. M., WEENING, J. J. (2000). Strong and Selective Glomerular Localization of CD134 Ligand and TNF Receptor-1 in Proliferative Lupus Nephritis. J. Am. Soc. Nephrol. 11: 1426-1438 [Abstract] [Full Text]  
• Herbein, G., O'brien, W. A. (2000). Tumor Necrosis Factor (TNF)-{alpha} and TNF Receptors in Viral Pathogenesis. Exp. Biol. Med. 223: 241-257 [Abstract] [Full Text]  
• Herrera, P. L., Harlan, D. M., Vassalli, P. (2000). A mouse CD8 T cell-mediated acute autoimmune diabetes independent of the perforin and Fas cytotoxic pathways: Possible role of membrane TNF. Proc. Natl. Acad. Sci. USA 97: 279-284 [Abstract] [Full Text]  
• Brito, B. E., O’Rourke, L. M., Pan, Y., Anglin, J., Planck, S. R., Rosenbaum, J. T. (1999). IL-1 and TNF Receptor-Deficient Mice Show Decreased Inflammation in an Immune Complex Model of Uveitis. IOVS 40: 2583-2589 [Abstract] [Full Text]  
• Xu, H., Sethi, J. K., Hotamisligil, G. S. (1999). Transmembrane Tumor Necrosis Factor (TNF)-alpha Inhibits Adipocyte Differentiation by Selectively Activating TNF Receptor 1. J. Biol. Chem. 274: 26287-26295 [Abstract] [Full Text]  
• Marshall, W. L., Brinkman, B. M. N., Ambrose, C. M., Pesavento, P. A., Uglialoro, A. M., Teng, E., Finberg, R. W., Browning, J. L., Goldfeld, A. E. (1999). Signaling Through the Lymphotoxin-{beta} Receptor Stimulates HIV-1 Replication Alone and in Cooperation with Soluble or Membrane-Bound TNF-{alpha}. J. Immunol. 162: 6016-6023 [Abstract] [Full Text]  
• Schutze, S., Machleidt, T., Adam, D., Schwandner, R., Wiegmann, K., Kruse, M.-L., Heinrich, M., Wickel, M., Kronke, M. (1999). Inhibition of Receptor Internalization by Monodansylcadaverine Selectively Blocks p55 Tumor Necrosis Factor Receptor Death Domain Signaling. J. Biol. Chem. 274: 10203-10212 [Abstract] [Full Text]  
• Aggarwal, S., Gollapudi, S., Gupta, S. (1999). Increased TNF-{alpha}-Induced Apoptosis in Lymphocytes from Aged Humans: Changes in TNF-{alpha} Receptor Expression and Activation of Caspases. J. Immunol. 162: 2154-2161 [Abstract] [Full Text]  
• Dellacasagrande, J., Capo, C., Raoult, D., Mege, J.-L. (1999). IFN-{gamma}-Mediated Control of Coxiella burnetii Survival in Monocytes: The Role of Cell Apoptosis and TNF. J. Immunol. 162: 2259-2265 [Abstract] [Full Text]  
• Page, D. M., Roberts, E. M., Peschon, J. J., Hedrick, S. M. (1998). TNF Receptor-Deficient Mice Reveal Striking Differences Between Several Models of Thymocyte Negative Selection. J. Immunol. 160: 120-133 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS