International Immunology, Vol. 5, No. 6, pp. 625-630,June 1993
© 1993 Japanese Society for Immunology
Activation interferes with the APO-1 pathway in mature human T cells
Tumorimmunology Program, German Cancer Research Center, Heidelberg Germany
1 Oncology/Immunology Section, University Children's Hospital Heidelberg, Germany
2 TNO Institute of Applied Radiobiology and Immunology Rijswijk, The Netherlands
Correspondence to: Correspondence to: P. H. Krammer
One of the mechanisms to terminate a specific immune response may involve elimination of antigen activated T cells by programmed cell death, apoptosis. Apoptosis in activated T cells may be induced via the TCR-CD3 complex or/and cell surface molecules like the APO-1 (Fas) antigen, a new member of the nerve growth factor/tumor necrosis factor receptor superfamily. To investigate apoptosis in activated T cells we studied expression of APO-1 and sensitivity to APO-1 mediated apoptosis in human peripheral T lymphocytes. APO-1 is not expressed on cord blood and the majority of resting T cells, but on activated T cells. One day activated T cells in culture showed activation induced resistance to apoptosis (ARA). However, after prolonged in vitro culture, 6 day activated T cells acquired sensitivity to activation induced sensitivity to apoptosis (ASA). Restimulation of the ASA+ activated T cells by triggering TCR-CD3 or CD2 induced prollferation and apoptosis in a fraction of the cells. In the surviving fraction of ASA+ activated T cells, however, this treatment reinduced a transient ARA+ phenotype. Thus, activation of resting mature T cells or restimulation of activated T cells may induce a translent resistance to apoptotic signals. Activation signals may interfere with the APO-1 pathway and may prevent elimination of activated T cells in the periphery (peripheral selection).
Keywords: apoptosis, activated T cells, sensitivity and resistance to apoptosis
Received 11 December 1992, accepted 22 February 1993.
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N. Moulian, C. Renvoize, C. Desodt, A. Serraf, and S. Berrih-Aknin Functional Fas Expression in Human Thymic Epithelial Cells Blood, April 15, 1999; 93(8): 2660 - 2670. [Abstract] [Full Text] [PDF]
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M. M. Di Somma, F. Somma, M. S. G. Montani, R. Mangiacasale, E. Cundari, and E. Piccolella TCR Engagement Regulates Differential Responsiveness of Human Memory T Cells to Fas (CD95)-Mediated Apoptosis J. Immunol., April 1, 1999; 162(7): 3851 - 3858. [Abstract] [Full Text] [PDF]
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M. Gaubin, M. Autiero, S. Basmaciogullari, D. Metivier, Z. Misehal, R. Culerrier, A. Oudin, J. Guardiola, and D. Piatier-Tonneau Potent Inhibition of CD4/TCR-Mediated T Cell Apoptosis by a CD4-Binding Glycoprotein Secreted from Breast Tumor and Seminal Vesicle Cells J. Immunol., March 1, 1999; 162(5): 2631 - 2638. [Abstract] [Full Text] [PDF]
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N. H. Kabra, D. Cado, and A. Winoto A Tailless Fas-FADD Death-Effector Domain Chimera Is Sufficient to Execute Fas Function in T Cells But Not B Cells of MRL-lpr/lpr Mice J. Immunol., March 1, 1999; 162(5): 2766 - 2774. [Abstract] [Full Text] [PDF]
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S. Jayaraman, M. Castro, M. O'Sullivan, M. J. Bragdon, and M. J. Holtzman Resistance to Fas-Mediated T Cell Apoptosis in Asthma J. Immunol., February 1, 1999; 162(3): 1717 - 1722. [Abstract] [Full Text] [PDF]
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C. Scaffidi, I. Schmitz, P. H. Krammer, and M. E. Peter The Role of c-FLIP in Modulation of CD95-induced Apoptosis J. Biol. Chem., January 15, 1999; 274(3): 1541 - 1548. [Abstract] [Full Text] [PDF]
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M. Sata and K. Walsh Endothelial Cell Apoptosis Induced by Oxidized LDL Is Associated with the Down-regulation of the Cellular Caspase Inhibitor FLIP J. Biol. Chem., December 11, 1998; 273(50): 33103 - 33106. [Abstract] [Full Text] [PDF]
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T. Kataoka, M. Schroter, M. Hahne, P. Schneider, M. Irmler, M. Thome, C. J. Froelich, and J. Tschopp FLIP Prevents Apoptosis Induced by Death Receptors But Not by Perforin/Granzyme B, Chemotherapeutic Drugs, and Gamma Irradiation J. Immunol., October 15, 1998; 161(8): 3936 - 3942. [Abstract] [Full Text] [PDF]
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D. Wesch, S. Marx, and D. Kabelitz Monocyte-Dependent Death of Freshly Isolated T Lymphocytes: Induction by Phorbolester and Mitogens and Differential Effects of Catalase J. Immunol., August 1, 1998; 161(3): 1248 - 1256. [Abstract] [Full Text] [PDF]
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E. Gardby, P. Lane, and N. Y. Lycke Requirements for B7-CD28 Costimulation in Mucosal IgA Responses: Paradoxes Observed in CTLA4-H{gamma}1 Transgenic Mice J. Immunol., July 1, 1998; 161(1): 49 - 59. [Abstract] [Full Text] [PDF]
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S. Fournel, E. Robinet, N. Bonnefoy-Berard, O. Assossou, M. Flacher, H. Waldmann, G. Bismuth, and J.-P. Revillard A Noncomitogenic CD2R Monoclonal Antibody Induces Apoptosis of Activated T Cells by a CD95/CD95-L-Dependent Pathway J. Immunol., May 1, 1998; 160(9): 4313 - 4321. [Abstract] [Full Text] [PDF]
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L. Genestier, S. Fournel, M. Flacher, O. Assossou, J.-P. Revillard, and N. Bonnefoy-Berard Induction of Fas (Apo-1, CD95)-Mediated Apoptosis of Activated Lymphocytes by Polyclonal Antithymocyte Globulins Blood, April 1, 1998; 91(7): 2360 - 2368. [Abstract] [Full Text] [PDF]
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T. H. Holmstrom, S. C. Chow, I. Elo, E. T. Coffey, S. Orrenius, L. Sistonen, and J. E. Eriksson Suppression of Fas/APO-1-Mediated Apoptosis by Mitogen-Activated Kinase Signaling J. Immunol., March 15, 1998; 160(6): 2626 - 2636. [Abstract] [Full Text] [PDF]
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J. D. McLeod, L. S. K. Walker, Y. I. Patel, G. Boulougouris, and D. M. Sansom Activation of Human T Cells with Superantigen (Staphylococcal Enterotoxin B) and CD28 Confers Resistance to Apoptosis via CD95 J. Immunol., March 1, 1998; 160(5): 2072 - 2079. [Abstract] [Full Text] [PDF]
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S. Aggarwal and S. Gupta Increased Apoptosis of T Cell Subsets in Aging Humans: Altered Expression of Fas (CD95), Fas Ligand, Bcl-2, and Bax J. Immunol., February 15, 1998; 160(4): 1627 - 1637. [Abstract] [Full Text] [PDF]
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N. Moulian, J. Bidault, F. Truffault, A. M. Yamamoto, P. Levasseur, and S. Berrih-Aknin Thymocyte Fas Expression Is Dysregulated in Myasthenia Gravis Patients With Anti-Acetylcholine Receptor Antibody Blood, May 1, 1997; 89(9): 3287 - 3295. [Abstract] [Full Text] [PDF]
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J. Allison, H. M. Georgiou, A. Strasser, and D. L. Vaux Transgenic expression of CD95 ligand on islet beta cells induces a granulocytic infiltration but does not confer immune privilege upon islet allografts PNAS, April 15, 1997; 94(8): 3943 - 3947. [Abstract] [Full Text] [PDF]
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J.-P. Truman, C. Choqueux, J. Tschopp, J. Vedrenne, F. Le Deist, D. Charron, and N. Mooney HLA Class II-Mediated Death Is Induced Via Fas/Fas Ligand Interactions in Human Splenic B Lymphocytes Blood, March 15, 1997; 89(6): 1996 - 2007. [Abstract] [Full Text] [PDF]
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A. Ponton, M.-Vér. Clément, and I. Stamenkovic The CD95 (APO-1/Fas) Receptor Activates NF-kappaB Independently of Its Cytotoxic Function J. Biol. Chem., April 12, 1996; 271(15): 8991 - 8995. [Abstract] [Full Text] [PDF]
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T Sato, S Irie, S Kitada, and J. Reed FAP-1: a protein tyrosine phosphatase that associates with Fas Science, April 21, 1995; 268(5209): 411 - 415. [Abstract] [PDF]
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S Nagata and P Golstein The Fas death factor Science, March 10, 1995; 267(5203): 1449 - 1456. [Abstract] [PDF]
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M. Gomez-Angelats, C. D. Bortner, and J. A. Cidlowski Protein Kinase C (PKC) Inhibits Fas Receptor-induced Apoptosis through Modulation of the Loss of K+ and Cell Shrinkage. A ROLE FOR PKC UPSTREAM OF CASPASES J. Biol. Chem., June 23, 2000; 275(26): 19609 - 19619. [Abstract] [Full Text] [PDF]
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