The Journal of Immunology, Vol 157, Issue 9 3845-3849, Copyright © 1996 by American Association of Immunologists

ARTICLES

Apoptosis signaling pathways in normal T cells: differential activity of Bcl-2 and IL-1beta-converting enzyme family protease inhibitors on glucocorticoid- and Fas-mediated cytotoxicity

MB Moreno, SA Memon and CM Zacharchuk
Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Fas-mediated apoptosis plays an important role in regulating the immune response in peripheral T cells. Restimulation of T cell blasts up- regulates Fas and Fas ligand expression, with subsequent interaction leading to cell death. Overexpression of Bcl-2 in tumor cells blocks apoptosis induced by many stimuli, but inhibition of Fas-mediated killing has not been consistently observed. To examine the behavior of Bcl-2 in normal cells, T cell blasts were transiently transfected with Bcl-2 and related gene products to determine the effect on apoptotic signaling. Transient overexpression of Bcl-2 in mouse and human T cell blasts did not block Fas-mediated apoptosis, whereas etoposide- and glucocorticoid-induced cytotoxicity was potently inhibited. Expression of Bcl-xL and adenovirus E1B 19K did not interfere with anti-Fas killing. In contrast, interleukin-1beta-converting enzyme family protease inhibitors Ac-DEVD-CHO and CrmA blocked Fas-mediated apoptosis. These results suggest that peripheral T cells use distinct apoptosis signaling pathways with differential sensitivity to Bcl-2 and interleukin-1beta-converting enzyme family protease inhibitors. Since T cells normally express Bcl-2 and Bcl-xL following activation, their inability to block Fas-mediated apoptosis may allow for the elimination of self-reactive cells and the appropriate regulation of immune responses.

This article has been cited by other articles:

				S. B. Wallach-Dayan, G. Izbicki, P. Y. Cohen, R. Gerstl-Golan, A. Fine, and R. Breuer Bleomycin initiates apoptosis of lung epithelial cells by ROS but not by Fas/FasL pathway Am J Physiol Lung Cell Mol Physiol, April 1, 2006; 290(4): L790 - L796. [Abstract] [Full Text] [PDF]

				M. Kondoh, I. Suzuki, M. Sato, F. Nagashima, S. Simizu, M. Harada, M. Fujii, H. Osada, Y. Asakawa, and Y. Watanabe Kaurene Diterpene Induces Apoptosis in Human Leukemia Cells Partly through a Caspase-8-Dependent Pathway J. Pharmacol. Exp. Ther., October 1, 2004; 311(1): 115 - 122. [Abstract] [Full Text] [PDF]

				S. Lepine, B. Lakatos, M.-P. Courageot, H. Le Stunff, J.-C. Sulpice, and F. Giraud Sphingosine Contributes to Glucocorticoid-Induced Apoptosis of Thymocytes Independently of the Mitochondrial Pathway J. Immunol., September 15, 2004; 173(6): 3783 - 3790. [Abstract] [Full Text] [PDF]

				W. Van Molle, G. Denecker, I. Rodriguez, P. Brouckaert, P. Vandenabeele, and C. Libert Activation of Caspases in Lethal Experimental Hepatitis and Prevention by Acute Phase Proteins J. Immunol., November 15, 1999; 163(10): 5235 - 5241. [Abstract] [Full Text] [PDF]

				L. C. Spender, E. J. Cannell, M. Hollyoake, B. Wensing, J. M. Gawn, M. Brimmell, G. Packham, and P. J. Farrell Control of Cell Cycle Entry and Apoptosis in B Lymphocytes Infected by Epstein-Barr Virus J. Virol., June 1, 1999; 73(6): 4678 - 4688. [Abstract] [Full Text]

				K. F. Izban, T. Wrone-Smith, E. D. Hsi, B. Schnitzer, M. E. Quevedo, and S. Alkan Characterization of the Interleukin-1ß-Converting Enzyme/Ced-3-Family Protease, Caspase-3/CPP32, in Hodgkin's Disease : Lack of Caspase-3 Expression in Nodular Lymphocyte Predominance Hodgkin's Disease Am. J. Pathol., May 1, 1999; 154(5): 1439 - 1447. [Abstract] [Full Text] [PDF]

				S. Wesselborg, I. H. Engels, E. Rossmann, M. Los, and K. Schulze-Osthoff Anticancer Drugs Induce Caspase-8/FLICE Activation and Apoptosis in the Absence of CD95 Receptor/Ligand Interaction Blood, May 1, 1999; 93(9): 3053 - 3063. [Abstract] [Full Text] [PDF]

				K. J. Ivins, J. K. Ivins, J. P. Sharp, and C. W. Cotman Multiple Pathways of Apoptosis in PC12 Cells. CrmA INHIBITS APOPTOSIS INDUCED BY beta -AMYLOID J. Biol. Chem., January 22, 1999; 274(4): 2107 - 2112. [Abstract] [Full Text] [PDF]

				P. R. Mittelstadt and J. D. Ashwell Cyclosporin A-Sensitive Transcription Factor Egr-3 Regulates Fas Ligand Expression Mol. Cell. Biol., July 1, 1998; 18(7): 3744 - 3751. [Abstract] [Full Text]

				K. Kim, C.-k. Lee, T. J. Sayers, K. Muegge, and S. K. Durum The Trophic Action of IL-7 on Pro-T Cells: Inhibition of Apoptosis of Pro-T1, -T2, and -T3 Cells Correlates with Bcl-2 and Bax Levels and Is Independent of Fas and p53 Pathways J. Immunol., June 15, 1998; 160(12): 5735 - 5741. [Abstract] [Full Text] [PDF]

				S. A. Memon, J.-z. Hou, M. B. Moreno, and C. M. Zacharchuk Cutting Edge: Apoptosis Induced by a Chimeric Fas/FLICE Receptor: Lack of Requirement for Fas- or FADD-Binding Proteins J. Immunol., March 1, 1998; 160(5): 2046 - 2049. [Abstract] [Full Text] [PDF]

				L. Van Parijs, A. Biuckians, and A. K. Abbas Functional Roles of Fas and Bcl-2-Regulated Apoptosis of T Lymphocytes J. Immunol., March 1, 1998; 160(5): 2065 - 2071. [Abstract] [Full Text] [PDF]

				P. L. Arscott, J. Knapp, M. Rymaszewski, J. L. Bartron, J. D. Bretz, N. W. T hompson, and J. R. Baker Jr. Fas (APO-1, CD95)-Mediated Apoptosis in Thyroid Cells Is Regulated by a Labile Protein Inhibitor Endocrinology, November 1, 1997; 138(11): 5019 - 5027. [Abstract] [Full Text] [PDF]

				C. M. Eischen, T. J. Kottke, L. M. Martins, G. S. Basi, J. S. Tung, W. C. Earnshaw, P. J. Leibson, and S. H. Kaufmann Comparison of Apoptosis in Wild-Type and Fas-Resistant Cells: Chemotherapy-Induced Apoptosis Is Not Dependent on Fas/Fas Ligand Interactions Blood, August 1, 1997; 90(3): 935 - 943. [Abstract] [Full Text] [PDF]

				S. Krajewski, R. D. Gascoyne, J. M. Zapata, M. Krajewska, S. Kitada, M. Chhanabhai, D. Horsman, K. Berean, L. D. Piro, I. Fugier-Vivier, et al. Immunolocalization of the ICE/Ced-3-Family Protease, CPP32 (Caspase-3), in Non-Hodgkin's Lymphomas, Chronic Lymphocytic Leukemias, and Reactive Lymph Nodes Blood, May 15, 1997; 89(10): 3817 - 3825. [Abstract] [Full Text] [PDF]