Direct Analysis of Individual Killer T Cells: Susceptibility of Target Cells to Lysis and Secretion of Hydrolytic Enzymes by CTL

  • D. Zagury
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 146)


T cell mediated lysis has been extensively studied using the standard chromium release test (1) which measures semi-quantitatively the activity of cytotoxic T lyphocyte (CTL) suspensions from in vivo (2, 3) and in vitro (4) experimental systems. As reviewed by Berke (5) and more recently by Henney (6, 7), biological conditions required for T cell mediated cytotoxicity (T CMC) were well defined and the lytic process was dissected into three succesive stages: A) Binding, which is dependent upon the specific recognition by effector cells (E) of sensitizing antigens carried by targets (T). E-T cell contact is a necessary step for target lysis. B) Lethal hit during which stage a lesion occurs on the target cell. This process is at once “the most interesting and most enigmatic,” (7) since we do not know yet the nature of the “hit.” One hypothesis indeed proposed that target cell destruction is caused by a soluble mediator secreted by the killer lymphocytes (8). C) Cytolysis which does not require the continuous presence of the effector cell. The target cell undergoes a series of membrane permeability alterations leading to cell destruction (5–7).


Target Cell Hydrolytic Enzyme Killer Cell Effector Cell Lytic Cycle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. (1).
    Brunner, K.T., Cerottini, J.C., and Chapuis, B., 1968. Quantitative assay of the lytic action of immune lymphoid cells on chromium-labeled allogenic targets in vitro; inhibition by isoantibody a,d by drugs. Immunology, 14, p. 181.PubMedGoogle Scholar
  2. (2).
    Brunner, K.T., Mauel, J., Rudolf, H., and Chapuis, B., 1970. Studies of allograft immunity in mice. Induction, development and in vitro assay of cellular immunity. Immunology, 18, p. 501.PubMedGoogle Scholar
  3. (3).
    Berke, G., Sullivan, K.A., and Amos, D.B., 1972, Rejection of ascites tumor allograft. I. - Isolation, characterization and in vitro reactivity of peritoneal lymphoid effector cells from BALB/c mice immune to EL4 leukosis. J. Exp. Med., 135, p. 1334.PubMedCrossRefGoogle Scholar
  4. (4).
    Hayry, P. and Defendi, V., 1970. Mixed lymphocyte cultures produced by effector cells; model in vitro for allograft rejection. Science, 168, p. 133.PubMedCrossRefGoogle Scholar
  5. (5).
    Berke, G. and Amos, D.B., 1973. Mechanism of Ijrmphocyte- mediated cytolysis; the IMC cycle and its role in transplantation immunity. Transplant. Rev., 17, p. 71.PubMedGoogle Scholar
  6. (6).
    Henney, Ch.S., 1977. T cell-mediated cytolysis: an overview of some current issues. Contemporary Topics in Immuno-Biology, ed. O. Stutman, Plenum Press, New York - London.Google Scholar
  7. (7).
    Henney, Ch. S., 1980. The mechanism of T-cell mediated lysis. Immunology Today, 1, p. 36.CrossRefGoogle Scholar
  8. (8).
    Granger, G.A. and Kolb, W.P., 1968. Lymphocyte in vitro cytotoxicity. Mechanisms of immune and non-immune small lymphocyte mediated target destruction. J. Immunol., 101, p. 111.PubMedGoogle Scholar
  9. (9).
    Zagury, D., Bernard, J., Thiernesse, N., Feldman, M., and Berke, G., 1975. Isolation and characterization of individual functional reactive cytotoxic-T-ljrmphocytes conjugation, killing and recycling at the single cell level. Eur. J. Immunol., 5, p. 818.CrossRefGoogle Scholar
  10. (10).
    Zagury, M., Fouchard, M., & Petit, 1979. Cytolyse a mediation cellulaire dépendante d’une immunisation contre des antigènes cellulaires; identification et numeration des cellules cytotoxiques. C.R. Acad. Sci., Paris, série D, 288, p. 1243.Google Scholar
  11. (11).
    Zagury, D., Fouchard, M., Morgan, D.A., and Cerottini, J.C., 1980. Enumeration of T effector cells mediating direct and or lectin dependant lysis. Immunology Letters, 1:335.CrossRefGoogle Scholar
  12. (12).
    Berke, G., Sullivan, K.A., and Amos, D.B., 1972. Rejection of ascite tumor allografts. I. - Isolation, characterization and in vitro reactivity of PEL from BALB/c mice Immune to EL4 leukosis. J. Exp. Med., 135, p. 1334.PubMedCrossRefGoogle Scholar
  13. (13).
    Nicolas, G., and Zagury, D., 1980. Etude par cryofracture de la zone de contact entre cellule cytolytique et cellule cible. Biol, cell., 3, P. 231.Google Scholar
  14. (14).
    Thiernesse, N., David A., Bernard J., Jeannesson P., and Zagury, D., 1977. Activite phosphatasique acide de la cellule T cytolytique au cours du processus de cytolyse. C.R. Acad. Sci., Paris, 285, p.713.Google Scholar
  15. (15).
    Jeannesson, P., Bernard, J., Thiernesse, N., Cerottini, J.C., Brochier, J., and Zagury, D., 1978. Isolation and characterization of single killer K cells from human peripheral blood. In “Human leukocyte differentiation: its application to cancer.” INSERM, Symposium n 8, B. Serrou and C. Rosenfeld, Elsevier, North-Holland Medical Press.Google Scholar
  16. (16).
    Zagury, D., D.A. MDrgan, and Fouchard, M., 1980. Evidence for cytotoxic functions in well-defined hisnan T cell clones. Biomedicine, 22. P. 272.Google Scholar
  17. (17).
    Zagury, D., Morgan D.A., andFouchard, M., 1981. Production of well-defined human T lymphocyte clones. I. - Monoclonal culture and functional cytotoxicity maturation. J. Immunol. Methods, 43, p. 67.PubMedCrossRefGoogle Scholar
  18. (18).
    Golstein, P., Svedmyr, E.A.J., and Wigzell, H., 1971. Cells mediating specific in vitro cytotoxicity. I. — Detection of receptor-bearing lymphocytes. J. Exp. Med., 134, p. 1385.PubMedCrossRefGoogle Scholar
  19. (19).
    Zagury, D., Bernard, J., Jeannesson, P., Thiernesse, N., and Cerottini, J.C., 1979. Studies on the mechanism of T cell- mediated lysis at the single effector cell level. I. - Kinetic analyses of lethal hits and target cell lysis in multicellular conjugates. J. Immunol., 123, p. 1604.PubMedGoogle Scholar
  20. (20).
    Martz, E., 1975. Early steps in specific tumor cell lysis by sensitized T lymphocytes. I. - Resolution and characterization. J. Imunol., 115, p. 261.Google Scholar
  21. (21).
    Bykovskaja, S.N., Rytenko, A.N., Renschenbach, M.O., and Bykovsky, A.F., 1978. Ultrastructural alteration of cytolytic T lymphocytes. II. - Morphogenesis of secretory granules and intracellular vacuoles. Cell. Immunol., 40, p. 175.PubMedCrossRefGoogle Scholar
  22. (22).
    Weissmann, G., Goldstein, I., Hoffstein, S., Chauvet, G., and Robineaux, R., 1975. Yin/Yang modulation of lysosomal enzyme release from polymorphonuclear leucocytes by cyclic nucleotides. In Part IV “Role of Inflammatory cells in the Destruction of Synovid Tissues.” Annals N.Y. Acad, of Sciences, 222, 253 and 750.CrossRefGoogle Scholar
  23. (23).
    Henney, Ch. S., and Lichtenstein, L.M., 1971. The role of cyclic AMP in the cytolytic activity of lymphocytes. J. Immunol., 107, p. 610PubMedGoogle Scholar
  24. (24).
    Zagury, D., Bernard, J., Thiernesse, N., and Benoist, H., 1976. “Killer cells in action.”Google Scholar
  25. (25).
    Mayer, M.M., 1977. Mechanisms of cytolysis by lymphocytes: a) a comparison with complement. J. Immunol., 119, p. 1195.PubMedGoogle Scholar
  26. (26).
    Wallach, D., and Revel, M., 1979. Hormonal protection of interferon-treated cells against double-stranded RNA induced cytolysis. FEBS Letters, 101, p. 364.PubMedCrossRefGoogle Scholar
  27. (27).
    Lindahl, P., Leary, P., and Gresser, I., 1972. Enhancement by Interferon of the specific cytotoxicity of sensitized lymphocytes. Proc. Natl. Acad. Sci., 60, p. 721.CrossRefGoogle Scholar
  28. (28).
    Trinchieri, G., Santoli, D., and Koprowski, H., 1978. Spontaneous CMC in Humans: Role of Interferon and Immunoglobulins. J. Immunol., 120, p. 1849.PubMedGoogle Scholar
  29. (29).
    Stewart, W.E. II, DeClerco, E., and DeSomer, P., 1973. Specificity of Interferon induced enhancement of cytotoxicity for double stranded RNA induced cytolysis. J. General Virology, 18, p. 237.CrossRefGoogle Scholar
  30. (30).
    Carpen, O., Virtanen, I., and Saksela, E., 1980. The cytotoxicity activity of human NK cells requires an intact secretóry apparatus. Cell. Immunol, (in press).Google Scholar
  31. (31).
    David, A., Bernard, J., Thiernesse, N., Nicolas, G., Cerottini, J.C., and Zagury, D., 1979. Le processus d’exo- cytose lysosomale localisée est-il responsable de I’action cytolytique des lymphocytes T tueurs? C.R. Acad. Sci., Paris, 288, p. 441.Google Scholar

Copyright information

© Plenum Press, New York 1982

Authors and Affiliations

  • D. Zagury
    • 1
    • 2
  1. 1.Laboratoire de Physiologie cellulaireUniversité Pierre et Marie CurieParis Cedex 05France
  2. 2.Laboratoire de CytologieInstitut Jean-GodinotReimsFrance

Personalised recommendations