The Mechanisms That Control the Proliferation and Activity of Cytolytic T Lymphocytes

  • Markus Nabholz


The discovery in 1975 that culture supernatants of mitogen-activated leukocyte populations contained a lymphocyte-specific growth factor [T-cell growth factor (TCGF) = interleukin 2 (IL-2)]1 provided the cornerstone for the development of cellular immunology in the last decade.


Antigenic Stimulation Cytolytic Activity Lymphocyte Clone Mitogenic Lectin Cell Growth Factor Receptor 
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  1. 1.
    Morgan, D. A., Ruscetti, F. W., and Gallo, R. C., 1976, Selective in vitro growth of T-lymphocytes from normal human bone marrows, Science 193:1007–1008.PubMedCrossRefGoogle Scholar
  2. 2.
    Coutinho, A., Larsson, E., Grönvik, K., and Andersson, J., 1979, Studies on T-lymphocyte activation. II. The target cells for concanavalin A-induced growth factors, Eur. J. Immunol. 9:587–592.PubMedCrossRefGoogle Scholar
  3. 3.
    Bonnard, G. D., Yasaka, K., and Jacobson, D., 1979, Ligand-activated T cell growth factor-induced proliferation: Absorption of T-cell growth factor by activated T-cells, J. Immunol. 123:2704–2708.PubMedGoogle Scholar
  4. 4.
    Robb, R. J., Munck, A., and Smith, K. A., 1981, T Cell growth factor receptors. Quantitation, specificity, and biological relevance, J. Exp. Med. 154:1455–1474.PubMedCrossRefGoogle Scholar
  5. 5.
    Leonard, W. J., Depper, J. M., Uchiyama, T., Smith, K. A., Waldmann, T. A., and Greene, W. C., 1982, A monoclonal antibody that appears to recognize the receptor for human T-cell growth factor; partial characterization of the receptor, Nature 300:267–269.PubMedCrossRefGoogle Scholar
  6. 6.
    Osawa, H., and Diamantstein, T., 1983, The characteristics of a monoclonal antibody that binds specifically to rat T lymphoblasts and inhibits IL-2 receptor functions, J. Immunol. 30:51–55.Google Scholar
  7. 7.
    Malek, T. R., Robb, R. J., and Shevach, E. M., 1983, Identification and initial characterization of a rat monoclonal antibody reactive with the murine interleukin 2 receptor-ligand complex, Proc. Natl. Acad. Sci. USA 80:5694–5698.PubMedCrossRefGoogle Scholar
  8. 8.
    Leonard, W. J., Deeper, J. M., Robb, R. J., Waldmann, T. A., and Greene, W. C., 1983, Characterization of the human receptor for T-cell growth factor, Proc. Natl. Acad. Sci. USA 80:6957–6961.PubMedCrossRefGoogle Scholar
  9. 9.
    Leonard, W. J., Depper, J. M., Crabtree, G. R., Rudikoff, S., Pumphrey, J., Robb, R. J., Krönke, M., Svetlic, P. B., Peffer, N. J., Waldmann, T. A., and Greene, W. C., 1984, Molecular cloning and expression of cDNAs for the human interleukin-2 receptor, Nature 311:626–631.PubMedCrossRefGoogle Scholar
  10. 10.
    Nikaido, T., Shimizu, A., Ishida, N., Sabe, H., Teshigawara, K., Maeda, M., Uchiyama, T., Yodoi, J., and Honjo, T., 1984, Molecular cloning of cDNA encoding human interleukin-2 receptor, Nature 311:631–635.PubMedCrossRefGoogle Scholar
  11. 11.
    Nabholz, M., and MacDonald, H. R., 1983, Cytolytic T lymphocytes. Annu. Rev. Immunol. 1:273–306.PubMedCrossRefGoogle Scholar
  12. 12.
    Möller, G. (ed.), 1982, Effects of anti-membrane antibodies on killer T cells, Immunol. Rev. 68:1–218.Google Scholar
  13. 13.
    Reinherz, E. L., Meuer, S. C., Fitzgerald, K. A., Hussey, R. E., Hodgdon, J. C., Acuto, O., and Schlossmann, S. F., 1983, Comparison of T3 associated 49/43 kD cell surface molecules on individual human T cell clones: Evidence for peptide variability in T cell receptor structure, Proc. Natl. Acad. Sci. USA 80:4104–4108.PubMedCrossRefGoogle Scholar
  14. 14.
    Smith, K. A., 1980, T-Cell growth factor, Immunol Rev. 51:336–357.Google Scholar
  15. 15.
    Larsson, E.-L., and Coutinho, A., 1979, The role of mitogenic lectins in T-cell triggering, Nature 280:239–241.PubMedCrossRefGoogle Scholar
  16. 16.
    Pledger, W. J., Stiles, C. D., Antoniades, H. N., and Scher, C. D., 1978, An ordered sequence of events is required before BALB/c-3T3 cells become committed to DNA synthesis, Proc. Natl. Acad. Sci. USA 75:2839–2843.PubMedCrossRefGoogle Scholar
  17. 17.
    Cantrell, D. A., and Smith, K. A., 1983, Transient expression of interleukin 2 receptors. Consequences for T cell growth, J. Exp. Med. 158:1895–1911.PubMedCrossRefGoogle Scholar
  18. 18.
    Zubler, R. H., Lowenthal, J. W., Erard, F., Hashimoto, N., Devos, R., and MacDonald, H. R., 1984, Activated B cells express receptors for, and proliferate in response to, pure interleukin 2, J. Exp. med. 160:1170–1183.PubMedCrossRefGoogle Scholar
  19. 19.
    Tsudo, M., Uchiyama, T., and Uchino, H., 1984, Expression of TAC antigen on activated normal human B cells, J. Exp. Med. 160:612–617.PubMedCrossRefGoogle Scholar
  20. 20.
    MacDonald, H. R., Ceredig, R., and Cerottini, J.-C., 1984, Heterogeneity of lymphokine production by T lymphocytes: Analysis of established clones and primary limiting dilution microcultures, in: Progress in Immunology V (Y. Yanraniura and T. Tada, eds.), Academic Press, New York, pp. 247–258.Google Scholar
  21. 21.
    Silva, A., MacDonald, H. R., Conzelmann, A., Corthésy, P., and Nabholz, M., 1983, Rat × mouse T-cell hybrids with inducible specific cytolytic activity, Immunol. Rev. 76:105–129.PubMedCrossRefGoogle Scholar
  22. 22.
    Cloyd, M. W., 1983, Characterization of target cells for MCF viruses in AKR mice, Cell 32:217–225.PubMedCrossRefGoogle Scholar
  23. 23.
    Gillis, S., Scheid, M., and Watson, J., 1980, Biochemical and biologic characterization of lymphocyte regulatory molecules. III. The isolation and phenotypic characterization of interleukin-2 producing T cell lymphomas, J. Immunol. 125:2570–2578.PubMedGoogle Scholar
  24. 24.
    Conzelmann, A., Corthésy, P., and Nabholz, M., 1982, Correlation between cytolytic activity, growth factor dependence and lectin resistance in cytolytic T cell hybrids, in: Isolation, Characterization and Utilization of T Lymphocyte Clones (C. G. Fathman and F. W. Fitch, eds.), Academic Press, New York, pp. 205–215.Google Scholar
  25. 25.
    Conzelmann, A., Silva, A., Cianfriglia, M., Tougne, C., Sekaly, R. P., and Nabholz, M., 1982, Correlated expression of TCGF-dependence, sensitivity to Vicia villosa lectin and cytolytic activity in hybrids between cytolytic T cells and T lymphomas, J. Exp. Med. 156:1335–1351.PubMedCrossRefGoogle Scholar
  26. 26.
    Ceredig, R., Sekaly, R. P., and MacDonald, H. R., 1983, Differentiation in vitro of lyt-2+ thymocytes from embryonic lyt-2- precursors, Nature 303:248–250.PubMedCrossRefGoogle Scholar
  27. 27.
    Mathieson, B. J., and Fowlkes, B. J., 1984, Cell surface antigen expression on thymocytes: Development and phenotypic differentiation of intrathymic subsets, Immunol. Rev. 82:141–173.PubMedCrossRefGoogle Scholar
  28. 28.
    Lowenthal, J. P., Tougne, C., MacDonald, H. R., Smith, K. A., and Nabholz, M., 1985, Antigenic stimulation regulates the expression of IL-2 receptors in a cytolytic T lymphocyte clone, J. Immunol. 134:931–939.PubMedGoogle Scholar
  29. 29.
    Andrew, M. E., Braciale, V. L., and Braciale, T. J., 1984, Regulation of interleukin 2 receptor expression of murine cytotoxic T lymphocyte clones, J. Immunol. 132:839–844.PubMedGoogle Scholar
  30. 30.
    Hemler, M. E., Brenner, M. B., McLean, J. M., and Strominger, J. L., Antigenic stimulation regulates the level of expression of interleukin 2 receptor on human T cells, Proc. Natl. Acad. Sci. USA 81:2172–2175.Google Scholar
  31. 31.
    Reske-Kunz, A. B., von Steldern, D., Rüde, E., Osawa, H., and Diamantstein, T., 1984, Interleukin 2 receptors on an insulin-specific T cell line: Dynamics of receptor expression, J. Immunol. 133:1356–1361.PubMedGoogle Scholar
  32. 32.
    Meuer, S. C., Hussey, R. E., Cantrell, D. A., Hodgdon, J. C., Schlossman, S. F., Smith, K. S., and Reinherz, E. L., 1984, Triggering of the T3-Ti antigen-receptor complex results in clonal T-cell proliferation through an interleukin 2-dependent autocrine pathway, Proc. Natl. Acad. Sci. USA 81:1509–1513.PubMedCrossRefGoogle Scholar
  33. 33.
    Hünig, T., Loos, M., and Schimpl, A., 1983, The role of accessory cells in polyclonal T cell activation. I. Both induction of interleukin-2 production and interleukin-2 responsiveness by concanavalin A are accessory cell dependent, Eur. J. Immunol. 13:1–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Erard, F., Corthésy, P., Nabholz, M., Lowenthal, J. W., Zaech, P., Plaetinck, C., and MacDonald, H. R., 1985, Interleukin 2 is both necessary and sufficient for the growth and differentiation of lectin-stimulated cytolytic T lymphocyte precursors, J. Immunol. 134:1644–1652.PubMedGoogle Scholar
  35. 35.
    Sekaly, R. P., MacDonald, H. R., Zaech, P., and Nabholz, M., 1982, Cell cycle regulation of cloned cytolytic T cells by T-cell growth factor: Analysis by flow microfluorometry, J. Immunol. 129:1407–1415.PubMedGoogle Scholar
  36. 36.
    Erard, F., Corthésy, P., Smith, K. A., Fiers, W., Conzelmann, A., and Nabholz, M., 1984, Characterization of soluble factors which induce the cytolytic activity and the expression of T cell growth factor receptors of a T cell hybrid, J. Exp. Med. 160:584–599.PubMedCrossRefGoogle Scholar
  37. 37.
    Conzelmann, A., Corthésy, P., Cianfriglia, M., Silva, A., and Nabholz, M., 1982, Hybrids between rat lymphoma and mouse T cells with inducible cytolytic activity, Nature 298:170–172.PubMedCrossRefGoogle Scholar
  38. 38.
    Robb, R. J., Greene, W. C., and Rusk, C. M., 1984, Low and high affinity cellular receptors for interleukin 2. Implications for the level of Tac antigen, J. Exp. Med. 160:1126–1146.PubMedCrossRefGoogle Scholar
  39. 39.
    Kaye, J., Gillis, S., Mizel, S. B., Shevach, E. M., Malek, T. R., Dinarello, C. A., Lachman, L. B., and Janeway, Jr., C. A., 1984, Growth of a cloned helper T cell line induced by a monoclonal antibody specific for the antigen receptor: Interleukin 1 is required for the expression of receptors for interleukin 2, J. Immunol. 133:1339–1345.PubMedGoogle Scholar
  40. 40.
    Kelso, A., and Glasebrook, A. L., 1984, Secretion of interleukin 2, macrophage-activating factor, interferon and colony-stimulation factor by alloreactive T lymphocyte clones, J. Immunol. 13:2924–2931.Google Scholar
  41. 41.
    Dennert, G., and Podack, E. R., 1983, Cytolysis by H-2 specific T killer cells, J. Exp. Med. 157:1483–1495.PubMedCrossRefGoogle Scholar
  42. 42.
    Podack, E. R., and Königsberg, P. Y., 1984, Cytolytic T-cell granules: Isolation, structural, biochemical and functional characterization, J. Exp. Med. 160:695–710.PubMedCrossRefGoogle Scholar
  43. 43.
    Henkart, P. A., Millard, P. J., Reynolds, C. W., and Henkart, M. P., 1984, Cytolytic activity of purified cytoplasmic granules from cytotoxic rat large granular lymphocyte tumors, J. Exp. Med. 160:75–93.PubMedCrossRefGoogle Scholar
  44. 44.
    Engers, H. D., and MacDonald, H. R., 1976, Generation of cytolytic T lymphocytes in vitro, in: Contemporary Topics in Immunobiology (W. O. Weigle, ed.), Plenum Press, New York, pp. 145–190.Google Scholar
  45. 45.
    Raulet, D. H., and Bevan, M. J., 1982, A differentiation factor required for the expression of cytotoxic T cell function, Nature 296:754–757.PubMedCrossRefGoogle Scholar
  46. 46.
    Wagner, H., Hardt, C., Rouse, B. T., Röllinghoff, M., Schenrich, P., and Pfizenmaier, K., 1982, Dissection of the proliferative and differentiate signals controlling murine cytotoxic T lymphocyte responses, J. Exp. Med. 155:1876–1881.PubMedCrossRefGoogle Scholar
  47. 47.
    Kanagawa, O., 1983, Three different signals are required for the induction of cytolytic T lymphocytes from resting precursors, J. Immunol. 131:606–610.PubMedGoogle Scholar
  48. 48.
    Männel, D. N., Falk, W., and Dröge, W., 1983, Induction of cytotoxic T cell function requires sequential action of three lymphokines, J. Immunol. 130:2508–2510.PubMedGoogle Scholar
  49. 49.
    Garman, R. D., and Fan, D. P., 1983, Characterization of helper factors distinct from interleukin-2, necessary for the generation of allospecific cytolytic T lymphocytes, J. Immunol. 130:756–762.PubMedGoogle Scholar
  50. 50.
    Finke, J. H., Scott, J., Gillis, S., and Hilfiker, M. L., 1983, Generation of alloreactive cytotoxic T lymphocytes: Evidence for a differentiation factor distinct from IL-2, J. Immunol. 130:763–767.PubMedGoogle Scholar
  51. 51.
    Nguyen, T., and Nabholz, M., 1985, Glucocorticoid resistance is a dominant trait in hybrids between cytolytic T-lymphocyte lines and AKR-thymomas, manuscript submitted.Google Scholar
  52. 52.
    Ceredig, R., Lowenthal, J. W., Nabholz, M., and MacDonald, H. R., 1985, Expression of Interleukin 2 receptors as a differentiation marker on intrathymic stem cells, Nature 314:98–109.PubMedCrossRefGoogle Scholar
  53. 53.
    Lowenthal, J. W., Zubler, R. H., Nabholz, M., and MacDonald, H. R., Similarities between Interleukin 2 receptor number and affinity on activated B and T lymphocytes, manuscript submitted.Google Scholar
  54. 54.
    Lowenthal, J. W., Corthesy, P., Tougue, C., Lees, R., MacDonald, H. R., and Nabholz, M., manuscript in preparation.Google Scholar
  55. 55.
    Masson, D., Corthesy, P., Nabholz, M., and Tschopp, J., 1984, Appearance of cytolytic granules upon induction of cytolitic activity in CTL-hybrids, manuscript submitted.Google Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Markus Nabholz
    • 1
  1. 1.Genetics UnitSwiss Institute for Experimental Cancer Research (ISREC)EpalingesSwitzerland

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