T-Cell-Mediated Cytolysis: An Overview of Some Current Issues

  • Christopher S. Henney
Part of the Contemporary Topics in Immunobiology book series (CTI, volume 7)


It is the purpose of this brief review to summarize some recent developments in our understanding of the mechanism of T-cell-mediated cytolysis. As is customary in this series, the account will be a rather personal one, and the “developments” to be discussed will center principally on observations made in this laboratory during the course of the last two years.


Target Cell Effector Cell Spleen Cell None None Cytolytic Activity 
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  1. Berke, G., and Fishelson, Z., 1975, Localization of aggregated cell surface antigens of target cells bound to cytotoxic T lymphocytes, J. Exp. Med. 142:1011.PubMedCrossRefGoogle Scholar
  2. Berke, G., and Gabison, D., 1975, Energy requirements of the binding and lytic steps of T lymphocyte-mediated cytolysis of leukemic cells in vitro, Eur. J. Immunol. 5:671.PubMedCrossRefGoogle Scholar
  3. Berke, G., Gabison, D., and Feldman, M., 1975, The frequency of effector cells in populations containing cytotoxic T lymphocytes, Eur. J. Immunol. 5:813.CrossRefGoogle Scholar
  4. Berke, G., Sullivan, K.A., and Amos, B., 1972, Rejection of ascites tumor allograft. I. Isolation, characterization and in vitro reactivity of peritoneal lymphoid effector cells from BALB/c immune mice to EL4 leukosis, J. Exp. Med. 135:1334.PubMedCrossRefGoogle Scholar
  5. Berke, G., Ax, W., Ginsburg, H., and Feldman, M., 1969, Graft rejection in tissue culture. II. Quantification of the lytic action on mouse fibroblasts by rat lymphocytes sensitized on mouse embryo monolayers, Immunology 16:643.PubMedGoogle Scholar
  6. Bevan, M., and Cohn, M.J., 1975, Cytotoxic effects of antigen and mitogen induced T cells on various targets, J. Immunol. 114:559.PubMedGoogle Scholar
  7. Biberfield, P., and Johansson, A., 1975, Contact areas of cytotoxic lymphocytes and target cells: An electron microscopic study, Exp. Cell Res. 94:79.CrossRefGoogle Scholar
  8. Binz, H., and Wigzell, H., 1975, Shared idiotypic determinants on B and T lymphocytes reactive against the same antigenic determinants. III. Physical fractionation of specific immunocompetent T lymphocytes by affinity chromatography using anti-idiotypic antibodies, J. Exp. Med. 152:1231.CrossRefGoogle Scholar
  9. Brunner, K.T., and Cerottini, J.-C., 1971, Cytotoxic lymphocytes as effector cells of cell-mediated cytotoxicity, in: Progress in Immunology, p. 385 (B. Amos, ed.), Academic Press, New York.Google Scholar
  10. Brunner, K.T., Mauel, J., Cerottini, J.-C., and Chapuis, B., Quantitative assay for the lytic action of immune lymphoid cells on 51Cr-labelled allogeneic target cells in vitro: Inhibition by isoantibody and by drugs, Immunology 14:181.Google Scholar
  11. Bubbers, J.E., and Henney, C.S., 1975a, Studies on the synthetic capacity and antigenic expression of glutaraldehyde fixed target cells, J. Immunol. 114:1126.PubMedGoogle Scholar
  12. Bubbers, J.E., and Henney, C.S., 1975b, Studies on the mechanism of lymphocyte-mediated cytolysis. V. The use of cytochalasins A and B to dissociate glucose transport from the lytic event, J. Immunol. 115:145.PubMedGoogle Scholar
  13. Cerottini, J.-C., and Brunner, K.T., 1974, Cell mediated cytotoxicity, allograft rejection and tumor immunity, Adv. Immunol. 18:67.PubMedCrossRefGoogle Scholar
  14. Cerottini, J.-C., Nordin, A.A., and Brunner, K.T., 1970a, In vitro cytotoxic activity of thymus cells sensitized to alloantigens. Nature (London) 227:72.CrossRefGoogle Scholar
  15. Cerottini, J.-C., Nordin, A.A., and Brunner, K.T., 1970b, Specific in vitro cytotoxicity to thymus derived lymphocytes sensitized to alloantigens, Nature (London) 228:1308.CrossRefGoogle Scholar
  16. Cerottini, J.-C., Engers, H.D., MacDonald, H.K., and Brunner, K.T., 1974, Generation of cytotoxic T lymphocytes in vitro. II. Effect of repeated exposure to alloantigens on the cytotoxic activity of long-term mixed leucocyte cultures, J. Exp. Med. 140:719.CrossRefGoogle Scholar
  17. Crone, M., Koch, C., and Simonsen, M., 1972, The elusive T cell receptor, Transplant Rev. 10:36.PubMedGoogle Scholar
  18. Ferluga, J., and Allison, A.C., 1974, Observations on the mechanism by which T-lympho-cytes exert cytotoxic effects, Nature (London) 250:673.CrossRefGoogle Scholar
  19. Ferluga, J., and Allison, A.C., 1975, Cytotoxicity of isolated plasma membranes from lymph node cells, Nature (London) 255:708.CrossRefGoogle Scholar
  20. Forman, J.C., and Kettman, J., 1976, Specificity of cytotoxic effector cells for hapten-modified targets, Fed. Proc. Fed. Amer. Soc. Exp. Biol. 35:474 (abstract).Google Scholar
  21. Forman, J.C., Mongar, J.L., and Gomperts, B.D., 1973, Calcium ionophores and the movement of calcium ions following the physiological stimulus to a secretory process, Nature (London) 245:249.CrossRefGoogle Scholar
  22. Frye, L.D., and Friou, G.J., 1975, Inhibition of mammalian cytotoxic cells by phosphatidylcholine and its analogue, Nature (London) 258:333.CrossRefGoogle Scholar
  23. Gately, M., Gately, C., Henney, C.S., and Mayer, M.M., 1975, Studies on lymphokines: The production of antibody of guinea pig lymphotoxin and its use to distinguish lympho-toxin from migration inhibitory factor and mitogenic factor, J. Immunol. 115:817.PubMedGoogle Scholar
  24. George, W.J., Poison, J.B., O’Toole, A.G., and Goldberg, N.D., 1970, Evaluation of guano-sine 3′5′ cyclic phosphate in rat heart after perfusion with acetylcholine, Proc. Natl. Acad. Sci. U.S.A. 66:398.PubMedCrossRefGoogle Scholar
  25. Golstein, P., 1974, Sensitivity of cytotoxic T cells to T cell-mediated cytotoxicity, Nature (London) 252:81.CrossRefGoogle Scholar
  26. Golstein, P., and Fewtrell, C., 1975, Functional fractionation of human cytotoxic cells using differences in their cation requirements, Nature (London) 255:491.CrossRefGoogle Scholar
  27. Golstein, P., and Gomperts, B.D., 1975, Non-T cell-mediated cytolysis requires Mg++ but not a Ca++: An argument against a conventional “stimulus-secretion” mechanism for cytolysis, J. Immunol. 114:1264.PubMedGoogle Scholar
  28. Golstein, P., and Smith, E.T., 1976, The lethal hit stage of mouse T and non-T cell-mediated cytolysis: Differences in cation requirements and characterization of an analytical “cation pulse” method, Eur. J. Immunol. 6:31.PubMedCrossRefGoogle Scholar
  29. Granger, G.A., and Kolb, W.P., 1968, Lymphocyte in vitro cytotoxicity: Mechanisms of immune and non-immune small lymphocyte mediated target cell destruction, J. Immunol. 101:111.PubMedGoogle Scholar
  30. Green, H., Barrow, P., and Goldberg, B., 1959a, Effect of antibody and complement on permeability control in ascites tumor cells and erythrocytes, J. Exp. Med. 110:699.PubMedCrossRefGoogle Scholar
  31. Green, H., Fleischer, R.A., Barrow, P., and Goldberg, B., 1959b, The cytotoxic action of immune gamma globulin and complement on Krebs ascites tumor cells. II. Chemical studies, J. Exp. Med. 109:511.PubMedCrossRefGoogle Scholar
  32. Hadden, J.W., Hadden, E.M., Haddox, M.K., and Goldberg, N.D., 1972, Guanosine 3′5′ cyclic monophosphate: A possible intracellular mediator of mitogenic influences in lymphocytes, Proc. Natl. Acad. Sci. U.S.A. 69:3024.PubMedCrossRefGoogle Scholar
  33. Henney, C.S., 1971, Quantitation of the cell-mediated immune response. I. The number of cytolytically active mouse lymphoid cells induced by immunization with allogeneic mastocytoma cells, J. Immunol. 107:1558.PubMedGoogle Scholar
  34. Henney, C.S., 1973a, Studies on the mechanism of T cell mediated cytolysis, Transplant Rev. 17:37.PubMedGoogle Scholar
  35. Henney, C.S. 1973b, Studies on the mechanism of lymphocyte-mediated cytolysis. II. The use of various target cell markers to study cytolytic events, J. Immunol. 110:73.PubMedGoogle Scholar
  36. Henney, C.S., 1974a, Estimation of the size of a T cell induced lytic lesion, Nature (London) 249:456.CrossRefGoogle Scholar
  37. Henney, C.S., 1974b, Relationships between cytolytic activity of thymus derived lymphocytes and cellular cyclic nucleotide concentrations, in: Cyclic AMP, Cell Growth and the Immune Response pp. 195–209 (W. Braun, C.W. Parker, and L.M. Lichtenstein, eds.), Springer-Verlag, New York.Google Scholar
  38. Henney, C.S., 1975, T cell mediated cytolysis: Consideration of the role of a soluble mediator, J. Reticuloendothel. Soc. 17:231.PubMedGoogle Scholar
  39. Henney, C.S., and Bubbers, J.E., 1973a, Antigen-T lymphocyte interactions: Inhibition by cytochalasin B, J. Immunol. 111:85.PubMedGoogle Scholar
  40. Henney, C.S., and Bubbers, J.E., 1973b, Studies on the mechanism of lymphocyte-mediated cytolysis. I. The role of divalent cations in cytolysis by T lymphocytes, J. Immunol. 110:63.PubMedGoogle Scholar
  41. Henney, C.S., and Lichtenstein, L.M., 1971, The role of cyclic AMP in the cytolytic activity of lymphocytes, J. Immunol. 107:610.PubMedGoogle Scholar
  42. Henney, C.S., and Mayer, M.M., 1971, Specific cytolytic activity of lymphocytes: Effect of antibodies against complement components C2, C3 and Cs, Cell. Immunol. 2:702.PubMedCrossRefGoogle Scholar
  43. Henney, C.S., Bourne, H.R., and Lichtenstein, L.M., 1972, The role of cyclic 3′5′-adenosine monophosphate in the cytolytic activity of lymphocytes, J. Immunol. 108:1526.PubMedGoogle Scholar
  44. Henney, C.S., Gaffney, J., and Bloom, B.R., 1974, On the relation of soluble mediators to T cell mediated cytolysis, J. Exp. Med. 140:837.PubMedCrossRefGoogle Scholar
  45. Henkart, P., and Blumenthal, R., 1975, Interaction of lymphocytes with lipid bilayer membranes: A mode for lymphocyte-mediated lysis of target cells, Proc. Natl. Acad. Sci. U.S.A. 72:2789.PubMedCrossRefGoogle Scholar
  46. Kamat, R., and Henney, C.S., 1975, Studies on T cell clonal expansion. I. Suppression of killer T cell production in vivo, J. Immunol. 115:1592.PubMedGoogle Scholar
  47. Kuppers, R.C., and Henney, C.S., 1976, Evidence for direct linkage between antigen recognition and lytic expression in effector T cells, J. Exp. Med. 143:684.PubMedCrossRefGoogle Scholar
  48. Lichtenstein, L.M., Gillespie, E., Bourne, H.R., and Henney, C.S., 1972, The effects of a series of prostaglandins on in vitro models of the allergic response and cellular immunity, Prostaglandins 2:519.PubMedCrossRefGoogle Scholar
  49. Lichtenstein, L.M., Henney, C.S., Bourne, H.R., and Greenough, W.B., 1973, The effect of cholera toxin on in vitro models of immediate and delayed hypersensitivity: Further evidence for the role of cAMP, J. Clin. Invest. 52:691.PubMedCrossRefGoogle Scholar
  50. MacDonald, H.R., 1975, Early detection of potentially lethal events in T cell-mediated cytolysis, Eur. J. Immunol. 5:251.PubMedCrossRefGoogle Scholar
  51. Mage, M.G., and McHugh, L.L., 1975, Specific partial depletion of graft vs. host activity by incubation and centrifugation of mouse spleen cells on allogeneic spleen cell monolayers, J. Immunol. 115:911.PubMedGoogle Scholar
  52. Martz, E., 1975, Early steps in specific tumor cell lysis by sensitized mouse T lymphocytes. I. Resolution and characterization, J. Immunol. 115:261.PubMedGoogle Scholar
  53. Martz, E., 1976a, Multiple target cell killing by the cytolytic T lymphocyte and the mechanism of cytotoxicity, Transplantation 21:5.PubMedCrossRefGoogle Scholar
  54. Martz, E., 1976b, Functional adhesion and the calcium requirement in T lymphocyte-mediated killing, Fed. Proc. Fed. Amer. Soc. Exp. Biol. 35:248 (abstract).Google Scholar
  55. Martz, E., and Benacerraf, B., 1973, An effector cell independent step in target cell lysis by sensitized mouse lymphocytes, J. Immunol. 111:1538.PubMedGoogle Scholar
  56. Martz, E., Burakoff, B., and Benacefraf, B., 1974, Interpretation of the sequential release of small and large molecules from tumor cells by low temperature during cytolysis mediated by immune T cells or complement, Proc. Natl. Acad. Sci. U.S.A. 71:177.PubMedCrossRefGoogle Scholar
  57. Mauel, J., Rudolf, H., Chapuis, B., and Brunner, K.T., 1970, Studies of allograft immunity in mice. II. Mechanism of target cell inactivation in vitro by sensitized lymphocytes, Immunology 18:517.PubMedGoogle Scholar
  58. Moller, E., 1965, Contact-induced cytotoxicity by lymphoid cells containing foreign isoanti-gens, Science 147:873.CrossRefGoogle Scholar
  59. Plaut, M., Lichtenstein, L.M., Gillespie, E., and Henney, C.S., 1973, Studies on the mechanism of lymphocyte mediated cytolysis. IV. Specificity of the histamine receptor on effector T cells, J. Immunol. 111:389.PubMedGoogle Scholar
  60. Plaut, M., Bubbers, J.E., and Henney, C.S., 1976, Studies on the mechanism of lymphocyte-mediated cytolysis. VII. Two stages in the T cell-mediated lytic cycle with distinct cation requirements, J. Immunol. 116:150.PubMedGoogle Scholar
  61. Rasmussen, H., 1970, Cell communication, calcium ion, and cyclic adenosine monophosphate, Science 170:404.PubMedCrossRefGoogle Scholar
  62. Rosenau, W., 1968, Target cell destruction, Fed. Proc. Fed. Amer. Soc. Exp. Biol. 27:34.Google Scholar
  63. Rubens, R.P., and Henney, C.S., 1977, Studies on the mechanism of lymphocyte-mediated cytolysis. VIII. The use of Con A to delineate a distinctive killer T cell subpopulation. J. Immunol. 118:180.PubMedGoogle Scholar
  64. Rubin, R.P., 1974, Calcium and the Secretory Process, Plenum Press, New York.Google Scholar
  65. Selin, D., Wallach, D.F.H., and Fischer, H., 1971, Intercellular communication in cell-mediated cytotoxicity. Fluorescein transfer between H-2d target cells and H-2 b lymphocytes in vitro, Eur. J. Immunol. 1:453.CrossRefGoogle Scholar
  66. Strom, T.B., Carpenter, C.B., Garovoy, M.R., Austen, K.F., Merrill, J.P., and Kaliner, M., 1973, The modulating influence of cyclic nucleotides upon lymphocyte-mediated cytotoxicity, J. Exp. Med. 138:381.PubMedCrossRefGoogle Scholar
  67. Stulting, R.D., and Berke, G., 1973, Nature of lymphocyte-tumor interaction. A general method for cellular immunoabsorption, J. Exp. Med. 137:932.PubMedCrossRefGoogle Scholar
  68. Sura, S.N., Chernyakhovskaya, Y.U., Kadaghidze, A.G., Fuks, B.B., and Svet-Moldavsky, G.J., 1967, Cytochemical study of interaction between lymphocytes and target cells in tissue culture, Exp. Cell Res. 48:656.PubMedCrossRefGoogle Scholar
  69. Thorn, R.M., 1974, Thesis, University of Pennsylvania.Google Scholar
  70. Thorn, R.M., and Henney, C.S., 1976a, Studies on the mechanism of lymphocyte-mediated cytolysis. VI. A reappraisal of the requirement for protein synthesis during T cell-mediated lysis, J. Immunol. 116:146.PubMedGoogle Scholar
  71. Thorn, R.M., and Henney, C.S., 1976b, Enumeration of specific cytotoxic T cells, Nature (London) 262:75.CrossRefGoogle Scholar
  72. Todd, R., 1975, Functional characterization of membrane components of cytotoxic peritoneal exudate T lymphocytes. II. Trypsin sensitivity of the killer cell receptor, Transplantation 20:314.PubMedCrossRefGoogle Scholar
  73. Wagner, H., and Feldman, M., 1972, Cell-mediated immune response in vitro. I. A new in vitro system for the generation of cell-mediated cytotoxic activity, Cell. Immunol. 3:405.PubMedCrossRefGoogle Scholar
  74. Wagner, H., and Rollinghoff, M., 1974, T cell-mediated cytotoxicity: Discrimination between antigen recognition, lethal hit and cytolysis phase, Eur. J. Immunol. 4:475.CrossRefGoogle Scholar
  75. Waterfield, J.D., Waterfield, E., and Moller, G., 1975, Lymphocyte-mediated cytotoxicity against tumor cells. I. Con A activated cytotoxic effector cells exhibit immunological specificity, Cell. Immunol. 17:392.PubMedCrossRefGoogle Scholar
  76. Wedner, H.J., Dankner, R., and Parker, C.W., 1975, Cyclic GMP and lectin-induced lymphocyte activation, J. Immunol. 115:1682.PubMedGoogle Scholar
  77. Werkele, H., Lonai, P., and Feldman, M., 1972, Fractionation of antigen-re active cells on a cellular immunoadsorbent: Factors determining recognition of antigens by T lymphocytes, Proc. Natl. Acad. Sci. U.S.A. 69:1620.CrossRefGoogle Scholar
  78. Wilson, D.B., 1965, Quantitative studies on the behavior of sensitized lymphocytes in vitro. I. Relationship of the degree of destriction of homologous target cells to the number of lymphocytes and to the time of contact in culture and consideration of the effects of isoimmune serum, J. Exp. Med. 122:143.PubMedCrossRefGoogle Scholar
  79. Zagury, D., Bernard, J., Thierness, N., Feldman, M., and Berke, G., 1975, Isolation and characterization of individual functionally reactive cytotoxic T lymphocytes: Conjugation, killing and recycling at the single cell level, Eur. J. Immunol. 5:818.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • Christopher S. Henney
    • 1
    • 2
  1. 1.Departments of Medicine and MicrobiologyJohns Hopkins University School of MedicineBaltimoreUSA
  2. 2.O’Neill Memorial Research LaboratoriesGood Samaritan HospitalBaltimoreUSA

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