J. Exp. Med., Volume 186, Number 11, December 1, 1997 1939-1944

BRIEF DEFINITIVE REPORT:
T Cell Receptor Signals Enhance Susceptibility to Fas-mediated Apoptosis

By Brian Wong, Joseph Arron, and Yongwon Choi^*

From the ^* Howard Hughes Medical Institute, The Rockefeller University, New York 10021

Fas(CD95) and its ligand (FasL) interaction plays a pivotal role in T cell receptor (TCR)-mediated apoptosis. However, the susceptibility of T cells to Fas-mediated apoptosis is tightly regulated during immune responses, a regulation which is thought to maintain the antigen-specificity of T cell apoptosis. Here we show that TCR stimulation enhances the induction of Fas-mediated apoptosis. In addition, using a mutant T cell hybridoma with impaired FasL expression, we show that the synergy provided by TCR stimulation can be mimicked by activators of PKC but not calcium influx. This effect cannot be inhibited by actinomycin D, suggesting that TCR stimulation leads to the alteration in preexisting signaling molecules to enhance Fas-mediated apoptosis. Our results therefore provide a mechanism of how Fas-FasL interactions lead to T cell death in an antigen-specific manner via repetitive antigen stimulation.

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

This article has been cited by other articles:

• Tatari-Calderone, Z., Brogdon, J. L., Tinsley, K. W., Ramezani, A., Leitenberg, D. (2005). CD4-Dependent Signaling Is Required for a Late Checkpoint during Th2 Development Associated with Resistance to Activation-Induced Cell Death. J. Immunol. 175: 5629-5636 [Abstract] [Full Text]  
• Williams, K A, Standfield, S D, Smith, J R, Coster, D J (2005). Corneal graft rejection occurs despite Fas ligand expression and apoptosis of infiltrating cells. Br. J. Ophthalmol. 89: 632-638 [Abstract] [Full Text]  
• Yu, X.-Z., Levin, S. D., Madrenas, J., Anasetti, C. (2004). Lck Is Required for Activation-Induced T Cell Death after TCR Ligation with Partial Agonists. J. Immunol. 172: 1437-1443 [Abstract] [Full Text]  
• Rho, J., Gong, S., Kim, N., Choi, Y. (2001). TDAG51 Is Not Essential for Fas/CD95 Regulation and Apoptosis In Vivo. Mol. Cell. Biol. 21: 8365-8370 [Abstract] [Full Text]  
• Wipasa, J., Xu, H., Stowers, A., Good, M. F. (2001). Apoptotic Deletion of Th Cells Specific for the 19-kDa Carboxyl-Terminal Fragment of Merozoite Surface Protein 1 During Malaria Infection. J. Immunol. 167: 3903-3909 [Abstract] [Full Text]  
• Pettersen, R. D., Bernard, G., Olafsen, M. K., Pourtein, M., Lie, S. O. (2001). CD99 Signals Caspase-Independent T Cell Death. J. Immunol. 166: 4931-4942 [Abstract] [Full Text]  
• Wu, B., Wu, J.-M., Miagkov, A., Adams, R. N., Levitsky, H. I., Drachman, D. B. (2001). Specific Immunotherapy by Genetically Engineered APCs: The ""Guided Missile"" Strategy. J. Immunol. 166: 4773-4779 [Abstract] [Full Text]  
• Frost, P. J., Butterfield, L. H., Dissette, V. B., Economou, J. S., Bonavida, B. (2001). Immunosensitization of Melanoma Tumor Cells to Non-MHC Fas-Mediated Killing by MART-1-Specific CTL Cultures. J. Immunol. 166: 3564-3573 [Abstract] [Full Text]  
• Carpenter, P. A., Pavlovic, S., Tso, J. Y., Press, O. W., Gooley, T., Yu, X.-Z., Anasetti, C. (2000). Non-Fc Receptor-Binding Humanized Anti-CD3 Antibodies Induce Apoptosis of Activated Human T Cells. J. Immunol. 165: 6205-6213 [Abstract] [Full Text]  
• Lee, I.-H., Li, W. P., Hisert, K. B., Ivashkiv, L. B. (1999). Inhibition of Interleukin 2 Signaling and Signal Transducer and Activator of Transcription (STAT)5 Activation during T Cell Receptor-mediated Feedback Inhibition of T Cell Expansion. JEM 190: 1263-1274 [Abstract] [Full Text]  
• Pettersen, R. D., Hestdal, K., Olafsen, M. K., Lie, S. O., Lindberg, F. P. (1999). CD47 Signals T Cell Death. J. Immunol. 162: 7031-7040 [Abstract] [Full Text]  
• Sato, K., Nagayama, H., Takahashi, T. A. (1999). Aberrant CD3- and CD28-Mediated Signaling Events in Cord Blood T Cells Are Associated with Dysfunctional Regulation of Fas Ligand-Mediated Cytotoxicity. J. Immunol. 162: 4464-4471 [Abstract] [Full Text]  
• Zaks, T. Z., Chappell, D. B., Rosenberg, S. A., Restifo, N. P. (1999). Fas-Mediated Suicide of Tumor-Reactive T Cells Following Activation by Specific Tumor: Selective Rescue by Caspase Inhibition. J. Immunol. 162: 3273-3279 [Abstract] [Full Text]  
• Spinozzi, F., Agea, E., Fizzotti, M., Bassotti, G., Russano, A., Droetto, S., Bistoni, O., Grignani, F., Bertotto, A. (1998). Role of T-helper type 2 cytokines in down-modulation of Fas mRNA and receptor on the surface of activated CD4+ T cells: molecular basis for the persistence of the allergic immune response. FASEB J. 12: 1747-1753 [Abstract] [Full Text]  
• Yeh, J.-H., Hsu, S.-C., Han, S.-H., Lai, M.-Z. (1998). Mitogen-activated Protein Kinase Kinase Antagonized Fas-associated Death Domain Protein-mediated Apoptosis by Induced FLICE-inhibitory Protein Expression. JEM 188: 1795-1802 [Abstract] [Full Text]  
• Wang, R., Zhang, L., Yin, D., Mufson, R. A., Shi, Y. (1998). Protein Kinase C Regulates Fas (CD95/APO-1) Expression. J. Immunol. 161: 2201-2207 [Abstract] [Full Text]  
• Collette, Y., Benziane, A., Razanajaona, D., Olive, D. (1998). Distinct Regulation of T-Cell Death by CD28 Depending on Both Its Aggregation and T-Cell Receptor Triggering: A Role for Fas-FasL. Blood 92: 1350-1363 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS