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Fas-Based T Cell-Mediated Cytotoxicity

  • Chapter
Pathways for Cytolysis

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 198))

Abstract

Phenomenological studies on T cell-mediated cytotoxicity in vitro have been extensively reviewed (Perlmann and Holm 1969; Cerottini and Brunner 1974; Golstein and Smith 1977; Henney 1977; Martz 1977; Berke 1980; Sanderson 1981; Henkart 1985; Berke 1989a; Young 1989; Tschopp and Nabholz 1990; Duke 1991; Golstein et al. 1991; Sitkovsky and Henkart 1993). Based on these studies, two major molecular pathways for the lethal hit stage of T cell-mediated cytotoxicity have been proposed. The first pathway involves granule exocytosis and perforin release and was detected about 10 years ago (Henkart 1985; Podack 1985). When a cytotoxic T lymphocyte (CTL) encounters a target cell, the channel-forming molecule perforin and serine-esterases from CTL granules are released at the interface between the CTL and the target cell. Perforin molecules then form channels within the target cell membrane, which, together with some contribution from serine-esterases (Shiver et al. 1992; Shi et al. 1992), lead to target cell death. The second pathway involves direct effector cell-target cell membrane interactions during which transduction of a signal within the target cell occurs leading to its death. Striking recent progress has led to demonstration of the use of both pathways by cytotoxic

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References

  • Alderson MR, Armitage RJ, Maraskovsky E, Tough TW, Roux E, Schooley K, Ramsdell F, Lynch DH (1993) Fas transduces activation signals in normal human T lymphocytes. J Exp Med 178: 2231–2235

    Article  PubMed  CAS  Google Scholar 

  • Berke G (1980) Interaction of cytotoxic T lymphocytes and target cells. Prog Allergy 27: 69–133

    PubMed  CAS  Google Scholar 

  • Berke G (1989a) Functions and mechanisms of lysis induced by cytotoxic T lymphocytes and natural killer cells. In: Paul WE (ed) Fundamental immunology, 2nd edn Raven, New York, pp 735–764

    Google Scholar 

  • Berke G (1989b) The cytolytic T lymphocyte and its mode of action Immunol Lett 20: 169–178

    Article  PubMed  CAS  Google Scholar 

  • Cerottini J-C, Brunner KT (1974) Cell-mediated cytotoxicity, allograft rejection, and tumor immunity Adv Immunol 18: 67–132

    Article  PubMed  CAS  Google Scholar 

  • Chang JCC, Zhang L, Edgerton TL, Kaplan AM (1990) Heterogeneity in direct cytotoxic function of L3T4 T cells: TH1 clones express higher cytotoxic activity to antigen-presenting cells than TH2 clones. J Immunol 145: 409–416

    PubMed  CAS  Google Scholar 

  • Clark WR, Ostergaard HL, Gorman K, Torbett BE (1988) Molecular mechanisms of CTL-mediated lysis: a cellular perspective. Immunol Rev 103: 37–51

    Article  PubMed  CAS  Google Scholar 

  • Cohen JJ (1991) Programmed cell death in the immune system. Adv Immunol 50: 55–83

    Article  PubMed  CAS  Google Scholar 

  • Cohen JJ, Duke RC, Chervenak R, Sellins KS, Olson LK (1985) DNA fragmentation in targets of CTL: an example of programmed cell death in the immune system. Adv Exp Med Biol 184: 493–508

    PubMed  CAS  Google Scholar 

  • Cohen PL, Eisenberg RA (1991) Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease. Annu Rev Immunol 9: 243–269

    Article  PubMed  CAS  Google Scholar 

  • Conzelmann A, Corthesy P, Cianfriglia M, Silva A, Nabholz M (1982) Hybrids between rat lymphoma and mouse T cells with inducible cytolytic activity. Nature 298: 170–172

    Article  PubMed  CAS  Google Scholar 

  • D’Adamio L, Awad K M, Reinherz EL (1993) Thymic and peripheral apoptosis of antigen-specific T cells might cooperate in establishing self tolerance. Eur J Immunol 23: 747–753

    Article  PubMed  Google Scholar 

  • Davidson WF, Dumont FJ, Bedigian HG, Fowlkes BJ, Morse HC III (1986) Phenotypic, functional, and molecular genetic comparisons of the abnormal lymphoid cells of C3H-lpr//prand C3H-gld/gld mice. J Immunol 136: 4075–4084

    PubMed  CAS  Google Scholar 

  • Debatin K-M, Goldmann CK, Bamford R, Waldmann TA, Krammer PH (1990) Monoclonal-antibody- mediated apoptosis in adult T-cell leukaemia. Lancet 335: 497–500

    Article  PubMed  CAS  Google Scholar 

  • Don MM, Ablett G, Bishop CJ, Bundesen PG, Donald KJ, Searle J, Kerr JFR (1977) Death of cells by apoptosis following attachment of specifically allergized lymphocytes in vitro. Aust J Exp Biol 55: 407–417

    Article  CAS  Google Scholar 

  • Duke RC (1991) Apoptosis in cell-mediated immunity. In: Tomei LD, Cope FO (eds) Apoptosis: the molecular basis of cell death. Cold Spring Harbor Laboratory Press, New York, pp 209–226

    Google Scholar 

  • Duke RC, Chervenak R, Cohen JJ (1983) Endogenous endonuclease-induced DNA fragmentation: an early event in cell-mediated cytolysis. Proc Natl Acad Sci USA 80: 6361–6365

    Article  PubMed  CAS  Google Scholar 

  • Duke RC, Persechini PM, Chang S, Liu C-C, Cohen JJ, Young JD-E (1989) Purified perforin induces target cell lysis but not DNA fragmentation. J Exp Med 170: 1451–1456

    Article  PubMed  CAS  Google Scholar 

  • Fitch FW, McKisic MD, Lancki DW, Gajewski TF (1993) Differential regulation of murine T lymphocyte subsets. Annu Rev Immunol 11: 29–48

    Article  PubMed  CAS  Google Scholar 

  • Golstein P, Smith ET (1977) Mechanism of T cell-mediated cytolysis: the lethal hit stage. Contemp Top Immunobiol 7: 273–300

    PubMed  CAS  Google Scholar 

  • Golstein P, Ojcius DM, Young JD-E (1991) Cell death mechanisms and the immune system. Immunol Rev 121: 29–65

    Article  PubMed  CAS  Google Scholar 

  • Golstein P, Mattei M-G, Foa C, Luciani M-F (1994) Molecular mechanisms of T lymphocyte cytotoxicity, with emphasis on the Fas pathway. In: Gregory CD (ed) Apoptosis and the immune response. Wiley, New York (in press)

    Google Scholar 

  • Graham A, Heyman I, Lumsden A (1993) Even-numbered rhombomeres control the apoptotic elimination of neural crest cells from odd-numbered rhombomeres in the chick hindbrain. Development 119: 233–245

    PubMed  CAS  Google Scholar 

  • Gromkowski SH, Brown TC, Masson D, Tschopp J (1988) Lack of DNA degradation in target cells lysed by granules derived from cytolytic T lymphocytes. J Immunol 141: 774–778 Hartley SB, Cooke MP, Fulcher DA, Harris AW, Cory S, Basten A, Goodnow CC (1993) Elimination of self-reactive B lymphocytes proceeds in two stages: arrested development and cell death. Cell 72: 325–335

    Google Scholar 

  • Henkart PA (1985) Mechanism of lymphocyte-mediated cytotoxicity. Annu Rev Immunol 3: 31–58

    Article  PubMed  CAS  Google Scholar 

  • Henney CS (1977) T-cell-mediated cytolysis: an overview of some current issues. Contemp Top Immunobiol 7: 245–272

    PubMed  CAS  Google Scholar 

  • Heusei JW, Wesselschmidt RL, Shresta S, Russell JH, Ley TJ (1994) Cytotoxic lymphocytes require granzyme B for the rapid induction of DNA fragmentation and apoptosis in allogeneic target cells. Cell 76: 977–987

    Article  Google Scholar 

  • Ishiura S, Matsuda K, Koizumi H, Tsukahara T, Arahata K, Sugita H (1990) Calcium is essential for both the membrane binding and lytic activity of pore-forming protein (perforin) from cytotoxic T- lymphocyte. Mol Immunol 27: 803–807

    Article  PubMed  CAS  Google Scholar 

  • Itoh N, Yonehara S, Ishii A, Yonehara M, Mizushima S-L, Sameshima M, Hase A, Seto Y, Nagata S (1991) The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 66: 233–243

    Article  PubMed  CAS  Google Scholar 

  • Ju S-T (1991) Distinct pathways of CD4 and CD8 cells induce rapid target DNA fragmentation. J Immunol 146: 812–818

    PubMed  CAS  Google Scholar 

  • Ju S-T, Ruddle NH, Strack P, Dorf ME, Dekruyff RH (1990) Expression of two distinct cytolytic mechanisms among murine CD4 subsets. J Immunol 144: 23–31

    PubMed  CAS  Google Scholar 

  • Kägi D, Ledermann B, Bürki K, Seiler P, Odermatt B, Olsen KJ, Podack ER, Zinkernagel RM, Hengartner H (1994a) Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice. Nature 369: 31–37

    Article  PubMed  Google Scholar 

  • Kägi D, Vignaux F, Ledermann B, Bürki K, Depraetere V, Nagata S, Hengartner H, Golstein P (1994b) Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity. Science 265: 528–530

    Article  PubMed  Google Scholar 

  • Kerr JFR, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26: 239–257

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi N, Hamamoto Y, Yamamoto N, Ishii A, Yonehara M, Yonehara S (1990) Anti-Fas monoclonal antibody is cytocidal to human immunodeficiency virus-infected cells without augmenting viral replication. Proc Natl Acad Sci USA 87: 9620–9624

    Article  PubMed  CAS  Google Scholar 

  • Lancki DW, Weiss A, Fitch FW (1987) Requirements for triggering of lysis by cytolytic T lymphocyte clones. J Immunol 138: 3646–3653

    PubMed  CAS  Google Scholar 

  • Lancki DW, Hsieh C-S, Fitch FW (1991) Mechanisms of lysis by cytotoxic T lymphocyte clones: lytic activity and gene expression in cloned antigen-specific CD4+ and CD8+ T lymphocytes. J Immunol 146: 3242–3249

    PubMed  CAS  Google Scholar 

  • Lang RA, Bishop JM (1993) Macrophages are required for cell death and tissue remodeling in the developing mouse eye. Cell 74: 453–462

    Article  PubMed  CAS  Google Scholar 

  • Liepins A, Faanes RB, Lifter J, Choi YS, De Harven E (1977) Ultrastructural changes during T- lymphocyte-mediated cytolysis. Cell Immunol 28: 109–124

    Article  PubMed  CAS  Google Scholar 

  • Luciani M-F, Golstein P (1994) Fas-based d1 OS-mediated cytotoxicity requires macromolecular synthesis for effector cell activation but not for target cell death. R Soc Philos Trans B 345: 303–309

    Article  CAS  Google Scholar 

  • MacLennan ICM, Gotch FM, Golstein P (1980) Limited specific T-cell mediated cytolysis in the absence of extracellular Ca++. Immunology 39: 109–117

    PubMed  CAS  Google Scholar 

  • Mapara MY, Bargou R, Zugck C, Dohner H, Ustaoglu F, Jonker RR, Krammer PH, Dorken B (1993) APO-1 mediated apoptosis or proliferation in human chronic B lymphocytic leukemia: correlation with bcl-2 oncogene expression. Eur J Immunol 23: 702–708

    Article  PubMed  CAS  Google Scholar 

  • Martz E (1977) Mechanism of specific tumor-cell lysis by alloimmune T lymphocytes: resolution and characterization of discrete steps in the cellular interaciton. Contemp Top Immunobiol 7: 301–361

    PubMed  CAS  Google Scholar 

  • Matter A (1979) Microcinematographic and electron microscopic analysis of target cell lysis induced by cytotoxic T lymphocytes. Immunology 36: 179–190

    PubMed  CAS  Google Scholar 

  • Miyawaki T, Uehara T, Nibu R, Tsuji T, Yachie A, Yonehara S, Taniguchi N (1992) Differential expression of apoptosis-related Fas antigen on lymphocyte subpopulations in human peripheral blood. J Immunol 149: 3753–3758

    PubMed  CAS  Google Scholar 

  • Oehm A, Behrmann I, Falk W, Pawlita M, Maier G, Klas C, Li-Weber M, Richards S, Dhein J, Trauth BC, Ponstingl H, Krammer PH (1992) Purification and molecular cloning of the APO-1 cell surface antigen, a member of the tumor necrosis factor/nerve growth factor receptor superfamily. Sequence identity with the Fas antigen. J Biol Chem 267: 10709–10715

    PubMed  CAS  Google Scholar 

  • Ostergaard HL, Kane KP, Mescher MF, Clark WR (1987) Cytotoxic T lymphocyte mediated lysis without release of serine esterase. Nature 330: 71–72

    Article  PubMed  CAS  Google Scholar 

  • Owen-Schaub LB, Yonehara S, Crump WL, III, Grimm EA (1992) DNA fragmentation and cell death is selectively triggered in activated human lymphocytes by Fas antigen engagement. Cell Immunol 140: 197–205

    Article  PubMed  CAS  Google Scholar 

  • Perlmann P, Holm G (1969) Cytotoxic effects of lymphoid cells in vitro. Adv Immunol 11: 117–193

    Article  PubMed  CAS  Google Scholar 

  • Podack ER (1985) Molecular mechanism of lymphocyte-mediated tumor cell lysis. Immunol Today 6: 21–27

    Article  CAS  Google Scholar 

  • Podack ER, Young JD-E, Cohn ZA (1985) Isolation and biochemical and functional characterization of perforin 1 from cytolytic T-cell granules. Proc Natl Acad Sci USA 82: 8629–8633

    Article  PubMed  CAS  Google Scholar 

  • Raff M C (1992) Social controls on cell survival and cell death. Nature 356: 397–400

    Article  PubMed  CAS  Google Scholar 

  • Ramsdell F, Seaman MS, Miller RE, Tough TW, Alderson MR, Lynch DH (1994) gld/gldmice are unable to express a functional ligand for Fas. Eur J Immunol 24: 928–933

    Google Scholar 

  • Rouvier E, Luciani M-F, Golstein P (1993) Fas involvement in Ca++-independent T cell-mediated cytotoxicity. J Exp Med 177: 195–200

    Article  PubMed  CAS  Google Scholar 

  • Russell JH (1983) Internal disintegration model of cytotoxic lymphocyte-induced target damage. Immunol Rev 72: 97–118

    Article  PubMed  CAS  Google Scholar 

  • Russell JH (1986) Phorbol-ester stimulated lysis of weak and non-specific target cells by cytotoxic T lymphocytes. J Immunol 136: 23–27

    PubMed  CAS  Google Scholar 

  • Russell JH, Masakovski V, Rucinsky T, Phillips G (1982) Mechanisms of immune lysis. III. Characterization of the nature and kinetics of the cytotoxic T lymphocyte-induced nuclear lesion in the target. J Immunol 128: 2087–2094

    PubMed  CAS  Google Scholar 

  • Russell JH, Wang R (1993) Autoimmune gld mutation uncouples suicide and cytokine/proliferation pathways in activated, mature T cells. Eur J Immunol 23: 2379–2382

    Article  CAS  Google Scholar 

  • Russell JH, Rush B, Weaver C, Wang R (1993) Mature T cells of autoimmune Ipr/lpr mice have a defect in antigen-stimulated suicide. Proc Nat Acad Sci USA 90: 4409–4413

    Article  PubMed  CAS  Google Scholar 

  • Sanderson CJ (1976) The mechanism of T cell mediated cytotoxicity. II. Morphological studies of cell death by time-lapse microcinematography. Proc R Soc Lond 192: 241–255

    Article  PubMed  CAS  Google Scholar 

  • Sanderson CJ (1981) The mechanism of lymphocyte-mediated cytotoxicity. Biol Rev 56: 153–197

    Article  PubMed  CAS  Google Scholar 

  • Schmid DS, Tite JP, Ruddle NH (1986) DNA fragmentation: manifestation of target cell destruction mediated by cytotoxic T-cell lines, lymphotoxin-secreting helper T-cell clones, and cell-free lymphotoxin-containing supernatant. Proc Natl Acad Sci USA 83: 1881–1885

    Article  PubMed  CAS  Google Scholar 

  • Shi L, Kraut RP, Aebersold R, Greenberg AH (1992) A natural killer cell granule protein that induces DNA fragmentation and apoptosis. J Exp Med 175: 553–566

    Article  PubMed  CAS  Google Scholar 

  • Shiver JW, Su L, Henkart PA (1992) Cytotoxicity with target DNA breakdown by rat basophilic leukemia cells expressing both cytolysin and granzyme A. Cell 71: 315–322

    Article  CAS  Google Scholar 

  • Sitkovsky M, Henkart P (1993) Cytotoxic cells. Birkhauser, Boston

    Google Scholar 

  • Smyth MJ, Norihisa Y, Ortaldo J R (1992) Multiple cytolytic mechanisms displayed by activated human eripheral blood T cell subsets. J Immunol 148: 55–62

    PubMed  CAS  Google Scholar 

  • Suda T, Nagata S (1994) Purification and characterization of the Fas-ligand that induces apoptosis. J Exp Med 179: 873–879

    Article  PubMed  CAS  Google Scholar 

  • Suda T, Takahashi T, Golstein P, Nagata S (1993) Molecular cloning and expression of the Fas ligand: a novel member of the tumor necrosis factor family. Cell 75: 1169–1178

    Article  PubMed  CAS  Google Scholar 

  • Sulston JE, Albertson DG, Thomson JN (1980) The Caenorhabditis elegans male: postembryonic development of nongonadal strucutres. Dev Biol 78: 542–576

    Article  PubMed  CAS  Google Scholar 

  • Takahashi T, Tanaka M, Brannan CI, Jenkins NA, Copeland NG, Suda T, Nagata S (1994) Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell 76: 969–976

    Article  PubMed  CAS  Google Scholar 

  • Tirosh R, Berke G (1985) T lymphocyte-mediated cytolysis as an excitatory process of the target. I. Evidence that the target may be the site of Ca++ action. Cell Immunol 95: 113–123

    Article  PubMed  CAS  Google Scholar 

  • Trauth BC, Klas C, Peters AMJ, Matzku S, Moller P, Falk W, Debatin K-M, Krammer PH (1989) Monoclonal antibody-mediated tumor regression by induction of apoptosis. Science 245: 301–305

    Article  PubMed  CAS  Google Scholar 

  • Trenn G, Takayama H, Sitkovsky MV (1987) Exocytosis of cytolytic granules may not be required for target cell lysis by cytotoxic T-lymphocytes. Nature 330: 72–74

    Article  PubMed  CAS  Google Scholar 

  • Tschopp J, Nabholz M (1990) Perforin-mediated target cell lysis by cytolytic T lymphocytes. Annu Rev Immunol 8: 279–302

    Article  PubMed  CAS  Google Scholar 

  • Vignaux F, Golstein P (1994) Fas-based lymphocyte-mediated cytotoxicity against syngeneic activated lymphocytes: a regulatory pathway? Eur J Immunol 24: 923–927

    Article  PubMed  CAS  Google Scholar 

  • Von Boehmer H, Hengartner H, Nabholz M, Lernhardt W, Schreier MH, Haas W (1979) Fine specificity of a continuously growing killer cell clone specific for H-Y antigen. Eur J Immunol 9: 592–597

    Article  Google Scholar 

  • Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S (1992a) Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356: 314–317

    Article  PubMed  CAS  Google Scholar 

  • Watanabe-Fukunaga R, Brannan CI, Itoh N, Yonehara S, Copeland NG, Jenkins NA, Nagata S (1992b) The cDNA structure, expression, and chromosomal assignment of the mouse Fas antigen. J Immunol 148: 1274–1279

    PubMed  CAS  Google Scholar 

  • Yonehara S, Ishii A, Yonehara M (1989) A cell-killing monoclonal antibody (Anti-Fas) to a cell surface antigen co-down regulated with the receptor of tumor necrosis factor. J Exp Med 169: 1747–1756

    Article  PubMed  CAS  Google Scholar 

  • Young JD-E (1989) Killing of target cells by lymphocytes: a mechanistic view. Physiol Rev 69: 250–314

    PubMed  CAS  Google Scholar 

  • Young JD-E, Clark WR, Liu C-C, Cohn ZA (1987a) A calcium- and perforin-independent pathway of killing mediated by murine cytolytic lymphocytes. J Exp Med 166: 1894–1899

    Article  PubMed  CAS  Google Scholar 

  • Young JD-E, Damiano A, Dinome MA, Leong LG, Cohn ZA (1987b) Dissociation of membrane binding and lytic activities of the lymphocyte pore-forming protein (perforin). J Exp Med 165: 1371–1382

    Article  PubMed  CAS  Google Scholar 

  • Young LHY, Klavinskis LS, Oldstone MBA, Young JD-E (1989) In vivo expression of perforin by CD8+ lymphocytes during an acute viral infection. J Exp Med 169: 2159–2171

    Article  PubMed  CAS  Google Scholar 

  • Zychlinsky A, Zheng L-M, Liu C-C, Young JD-E (1991) Cytotoxic lymphocytes induce both apoptosis and necrosis in target cells. J Immunol 146: 393–400

    PubMed  CAS  Google Scholar 

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  1. Centre d’Immunologie INSERM-CNRS de Marseille-Luminy, Case 906, 13288, Marseille Cedex 9, France

    P. Golstein

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  1. Basel Institute of Immunology, Grenzacherstr. 487, 4005, Basel, Switzerland

    Gillian M. Griffiths

  2. Department of Biochemistry, University of Lausanne, Ch. Boveresses 155, 1066, Epalinges/Lausanne, Switzerland

    Jürg Tschopp

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Golstein, P. (1995). Fas-Based T Cell-Mediated Cytotoxicity. In: Griffiths, G.M., Tschopp, J. (eds) Pathways for Cytolysis. Current Topics in Microbiology and Immunology, vol 198. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79414-8_2

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  • DOI: https://doi.org/10.1007/978-3-642-79414-8_2

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