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Granule-Mediated Cytolysis of Target Cells

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Cytotoxic Effector Mechanisms

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 140))

Abstract

The lysis of target cells attacked by cytotoxic T cells appears to be caused by two possibly related phenomena, namely the formation of transmembrane pores in the target cell’s membrane and the cleavage and release of the target cell’s nuclear DNA. At present it is not entirely clear how these effects are mediated at a molecular level. However, in the past few years, concepts have evolved and been experimentally tested that allow the formulation of a comprehensive hypothesis to explain the main steps of lymphocyte-mediated cytolysis (Podack 1985; Henkart 1985). This said, it should be pointed out, however, that at the time of writing none of the effector molecules discussed below can be unequivocally linked to the cytolytic process, when intact killer cells lyse a target cell.

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References

  • Berke G, Rosen D (1987) Are lytic granules and perforin 1 thereof involved in lysis induced by in vivo primed, peritoneal exudate CTL? Transplant Proc 19:412

    PubMed  CAS  Google Scholar 

  • Carney DF, Koski CL, Shin ML (1985) Elimination of terminal complement intermediates from the plasma membrane of nucleated cells: the rate of disappearance differs for cells carrying C5b-7 or C5b-8 or a mixture of C5b-8 with a limited number of C5b-9. J Immunol 134:1804

    PubMed  CAS  Google Scholar 

  • Dennert G, Podack ER (1983) Cytolysis by H2 specific T-killer cells: assembly of tubular complexes during the lytic reaction. J Exp Med 157:1483–1495

    Article  PubMed  CAS  Google Scholar 

  • Dennert G, Anderson CG, Psocharka G (1987) High activity of Nα-benzyloxycarbonyl-L-lysine thiobenzylester serine esterase and cytolytic perforin in cloned cell lines is not demonstrable in vivoinduced cytotoxic effector cells. Proc Natl Acad Sci USA 84:5004

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Duke RC, Cohen JJ, Chervenak R (1986) Differences in target cell DNA fragmentation induced by mouse cytotoxic T lymphocytes and natural killer cells. J Immunol 137:1442

    PubMed  CAS  Google Scholar 

  • Geiger B, Rosen D, Berke G (1982) Spatial relationships of MTOC and the contact area of CTLs and target cells. J Cell Biol 95:137

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Henkart P, Millard P, Reynolds C, Henkart M (1984) Cytolytic activity of purified cytoplasmic granules from cytotoxic rat LGL tumors. J Exp Med 160:75

    Article  PubMed  CAS  Google Scholar 

  • Howell DM, Martz E (1987) The degree of CTL-induced DNA solubilization is not determined by the human vs. mouse origin of the target cell. J Immunol 138:2087

    Google Scholar 

  • Imboden JB, Stobo JD (1985) Transmembrane signalling by the T-cell antigen receptor. Perturbation of T3-antigen receptor complex generates inositol phosphates and releases calcium ions from intracellular stores. J Exp Med 161:446

    Article  PubMed  CAS  Google Scholar 

  • Konigsberg PJ, Podack ER (1986) DNA damage of target cells by cytolytic T-cell granules. J Cell Biochem [Suppl] 10B:85

    Google Scholar 

  • Konigsberg PY, Podack ER (1985) Target cell DNA-fragmentation induced by cytolytic T-cell granules. J Leukocyte Biol 38:109

    Google Scholar 

  • Kupfer A, Dennert G, Singer SJ (1985) The reorientation of the Golgi apparatus and the MTOC in the cytotoxic effector cell is a prerequisite in the lysis of bound target cells. J Mol Cell Immunol 2:37

    PubMed  CAS  Google Scholar 

  • Liu CC, Steffen M, King F, Young JDE (1987) Identification, isolation, and characterization of a novel cytotoxin in murine cytolytic lymphocytes. Cell 51:393

    Article  PubMed  CAS  Google Scholar 

  • Masson D, Tschopp J (1985) Isolation of a lytic, pore-forming protein (perforin) from cytolytic T-lymphocytes. J Biol Chem 260:9069

    PubMed  CAS  Google Scholar 

  • Munger WE, Berrelei G, Henkart PH (1987) Granule exocytosis by cytotoxic T-lymphocytes generated in vivo. Ann Inst Pasteur 138:301

    Article  CAS  Google Scholar 

  • Ostergaard H, Clark WR (1987) The role of Ca in activation of mature cytotoxic T-lymphocytes for lysis. J Immunol 139:3573

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Podack ER, Dennert G (1983) Cell mediated cytolysis: assembly of two types of tubules with putative cytolytic function by cloned natural killer cells. Nature 302:442–445

    Article  PubMed  CAS  Google Scholar 

  • Podack ER, Konigsberg PJ (1984) Cytolytic T-cell granules. Isolation, structural, biochemical, and functional characterization. J Exp Med 160:695

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Russel JH, Dobos CB (1980) Mechanism of immune lysis. II. CTL-induced nuclear disintegration begins within minutes of cell contact. J Immunol 125:1256

    Google Scholar 

  • Schmid DS. Tite JP, Ruddle NM (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

    Google Scholar 

  • Schmidt RE, MacDermott RP, Bartley G, Bertovitch M, Amato DA, Austen KF, Schlossman SF, Stevens RL, Ritz J (1985) Specific release of proteoglycans from human natural killer cells during target cell lysis. Nature 318:289

    Article  PubMed  CAS  Google Scholar 

  • Shipley WU, Baker AR, Colten H (1971) DNA degradation in mammalian cells following complement mediated cytolysis. J Immunol 106:576

    PubMed  CAS  Google Scholar 

  • Takayama M, Trenn G, Humphrey W, Bluestone J, Henkart P, Sitkovsky M (1987) Antigen receptor triggered secretion of a trypsin like esterase from cytotoxic T-lymphocytes. J Immunol 138:566

    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

    Article  PubMed  CAS  Google Scholar 

  • Ucker D (1987) Cytotoxic T lymphocytes and glucocorticoids activate an endogenous suicide process in target cells. Nature 327:62

    Article  PubMed  CAS  Google Scholar 

  • Yannelli JR, Sullivan JA, Mandel GL, Engelhard VM (1986) Reorientation and fusion of cytotoxic T-lymphocyte granules after interaction with target cells as determined by high resolution cinemicrography. J Immunol 136:377

    PubMed  CAS  Google Scholar 

  • Young JDE, Cohn ZA, Podack ER (1986) The ninth component of cytotoxic T-cells: structural and functional homologies. Science 233:184–190

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL, 33101, USA

    E. R. Podack

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  1. E. R. Podack
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Editors and Affiliations

  1. Department of Microbiology and Immunology, University of Miami School of Medicine, P.O. Box 016960(R-138), Miami, FL, 33101, USA

    Eckhard R. Podack M.D.

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© 1988 Springer-Verlag Berlin · Heidelberg

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Podack, E.R. (1988). Granule-Mediated Cytolysis of Target Cells. In: Podack, E.R. (eds) Cytotoxic Effector Mechanisms. Current Topics in Microbiology and Immunology, vol 140. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-73911-8_1

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  • DOI: https://doi.org/10.1007/978-3-642-73911-8_1

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-73913-2

  • Online ISBN: 978-3-642-73911-8

  • eBook Packages: Springer Book Archive

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