Continuous Cytotoxic T-Cell Lines

  • Kendall A. Smith
Part of the Contemporary Topics in Immunobiology book series (CTI, volume 11)


Recently, it was reported that it was possible to maintain normal human T lymphocytes in continuous exponential proliferative culture with the aid of a T-cell growth factor (TCGF) derived from lectin-stimulated peripheral blood mononuclear cells (Morgan et al., 1976; Ruscetti et al., 1977). Subsequently, we (Gillis and Smith, 1977; Gillis et al., 1978a; Baker et al., 1979) and others (Rosenberg et al., 1978; Strausser and Rosenberg, 1978; Nabholz et al., 1978) found that antigen-specific cytolytic T cells could be selected, maintained, and cloned in the presence of TCGF (IL2).* The discovery that such cytolytic T-lymphocyte lines (CTLL) were completely dependent upon TCGF (IL2) for their growth allowed for the development of a rapid, sensitive microassay for this mitogenic factor (Gillis et al., 1978b). This development, in turn, provided the means to perform detailed experimentation directed toward a definition of the biochemical and biological characteristics of TCGF(IL2). The results of these experiments, summarized in this chapter, suggest that the ability to culture functional monoclonal T cells will provide the means leading to an increased understanding of the T-cell immune response, in much the same way that the ability to culture immunoglobulin-secreting plasmacytoma cells has contributed to our understanding of the B-cell immune response.


Conditioned Medium Mixed Lymphocyte Culture Retard Tumor Growth Murine Spleen Cell Syngeneic Tumor Cell 
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  1. Baker, P. E., Gillis, S., Ferm, M. M., and Smith, K. A., 1978, The effect of T-cell growth factor on the generation of cytolytic T-cells, J. Immunol. 121: 2168–2173.PubMedGoogle Scholar
  2. Baker, P. E., Gillis, S., and Smith, K. A., 1979, Monoclonal cytolytic T-cell lines, J. Exp. Med. 149: 273–278.PubMedCrossRefGoogle Scholar
  3. Bernstein, I. D., 1977, Passive transfer of systemic tumor immunity with cells generated in vitro by a secondary immune response to a syngeneic rat Gross virus-induced lymphoma, J. Immunol. 118: 122–128.PubMedGoogle Scholar
  4. Billingham, R. E., Krohn, P. L., and Medawar, 1951, Effect of cortisone on survival of skin homografts in rabbits, Br. Med. J. 5: 4716.Google Scholar
  5. Cheever, M. A., Kempf, R. A., and Fefer, A., 1977, Tumor neutralization, immunotherapy, and chemoimmunotherapy of a Friend leukemia with cells secondarily sensitized in vitro, J. Immunol. 119: 714–718.PubMedGoogle Scholar
  6. Evans, R. L., Faldetta, T. J., Humphreys, R. E., Pratt, D. M., Yunis, E. J., and Schlossman, S. F., 1978, Peripheral human T-cells sensitized in mixed leukocyte culture synthesize and express la-like antigens, J. Exp. Med. 148: 1440–1445.PubMedCrossRefGoogle Scholar
  7. Fu, S. M., Chiorazzi, N., Wang, C. Y., Montazeri, G., Kunkel, H. G., Ko, H. S., and Gottlieb, A. B., 1978, Ia-bearing T-lymphocytes in man. Their identification and role in the generation of alloantigeneic helper activity, J. Exp. Med. 148: 1423–1428.PubMedCrossRefGoogle Scholar
  8. Gillis, S., and Smith, K. A., 1977, Long-term culture of tumor-specific cytotoxic T-cells, Nature (London) 268: 154–156.CrossRefGoogle Scholar
  9. Gillis, S., Baker, P. E., Ruscetti, F. W., and Smith K. A., 1978a, Long-term culture of human antigen-specific cytotoxic T-cell lines, J. Exp. Med. 148: 1093–1098.PubMedCrossRefGoogle Scholar
  10. Gillis, S., Ferm, M. M., Ou, W., and Smith, K. A., 1978b, T-cell growth factor: Parameters of production and a quantitative microassay for activity, J. Immunol. 120: 2027–2032.PubMedGoogle Scholar
  11. Gillis, S., Baker, P. E., Union, N. A., and Smith, K. A., 1979a, The in vitro generation and sustained culture of nude mouse cytolytic T-lymphocytes, J. Exp. Med. 149: 1460–1474.PubMedCrossRefGoogle Scholar
  12. Gillis, S., Crabtree, G. R., and Smith, K. A., 1979b, Glucocorticoid-induced inhibition of T-cell growth factor production. I. The effect on mitogen-induced lymphocyte proliferation, J. Immunol. 123: 1624–1631.PubMedGoogle Scholar
  13. Gillis, S., Crabtree, G. R., and Smith, K. A., 1979c, Glucocorticoid-induced inhibition of T-cell growth factor production. II. The effect on the in vitro generation of cytolytic T-cells. J. Immunol. 123: 1632–1638.PubMedGoogle Scholar
  14. Jordan, C. W., 1972, Basis for the probit analysis of an interferon plaque reduction assay, J. Gen. Virol. 14: 49.PubMedCrossRefGoogle Scholar
  15. Larsson, E. L., and Coutinho, A., 1979, The role of mitogenic lectins in T-cell triggering, Nature (London) 280: 239–241.CrossRefGoogle Scholar
  16. Medawar, P. B., and Sparrow, E. M., 1956, The effects of adrenocortical hormones, adrenocorticotrophic hormone and pregnancy on skin transplantation immunity in mice, J. Endocrinol. 14: 230.CrossRefGoogle Scholar
  17. Metzgar, R. S., Bertoglio, J., Anderson, J. K., Bonnard, G. D., and Ruscetti, F. W., 1979, Detection of HLA-DRw (Ia-like) antigens on human T-lymphocytes grown in tissue culture, J. Immunol. 122: 949.PubMedGoogle Scholar
  18. 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
  19. Nabholz, M., Engers, H. D., Callovo, D., and North, M., 1978, Cloned T-cell lines with specific cytolytic activity, in: Current Topics in Microbiology and Immunology, Vol. 81 ( F. Melchers, M. Potter, and N. Warner, eds.), p. 176, Springer-Verlag, New York.Google Scholar
  20. Nowell, P. C., 1961, Inhibition of human leukocyte mitosis by prednisolone in vitro, Cancer Res. 21: 1518.PubMedGoogle Scholar
  21. Rollinghoff, M., and Wagner, H., 1973, In vivo protection against murine plasma cell tumor growth by in vitro activated syngeneic lymphocytes, J. Natl. Cancer Inst. 51: 1317.PubMedGoogle Scholar
  22. Rosenberg, S. A., Schwarz, S., and Spiess, P. J., 1978, In vitro growth of mutine T-cells. II. Growth of in vitro sensitized cells cytotoxic for alloantigens, J. Immunol. 121: 1951–1955.PubMedGoogle Scholar
  23. Ruscetti, F. W., Morgan, D. A., and Gallo, R. C., 1977, Functional and morphologic charac- terization of human T-cells continuously grown in vitro, J. Immunol. 119: 131–138.PubMedGoogle Scholar
  24. Schreier, M. H., and Tees, R., 1980, Clonal induction of helper T cells: Conversion of specific signals into non-specific signals, Int. Arch. Allergy Appl. Immunol. 61: 227–237.PubMedCrossRefGoogle Scholar
  25. Smith, K. A., Crabtree, G. R., Kennedy, S. J., and Munck, A. U., 1977, Glucocorticoid receptors and glucocorticoid sensitivity of mitogen stimulated and unstimulated human lymphocytes. Nature (London) 269: 523–526.CrossRefGoogle Scholar
  26. Smith, K. A., Gillis, S., and Baker, P. E., 1979a, The Immunotherapeutic utility of cytotoxic T-lymphocyte lines, Proc. Am. Assoc. Cancer Res. 20: 93.Google Scholar
  27. Smith, K. A., Gillis, S., and Baker, P. E., 1979b, The role of soluble factors in the regulation of T-cell immune reactivity, in: The Molecular Basis of Immune Cell Function ( J. G. Kaplan, ed.), pp. 223–237, Elsevier-North Holland, Amsterdam.Google Scholar
  28. Smith, K. A., Gillis S., Baker, P. E., McKenzie, D., and Ruscetti, F. W., 1980a, T-cell growth factor mediated T-cell proliferation, Ann. N.Y. Acad. Sci. 332: 423–432.CrossRefGoogle Scholar
  29. Smith, K. A., Baker, P. E., Gillis, S., and Ruscetti, F. W., 1980b, Functional and molecular characteristics of T-cell growth factor, Mol. Immunol. (in press).Google Scholar
  30. Strausser, G. L., and Rosenberg, S. A., 1978, In vitro growth of cytotoxic human lymphocytes. I. Growth of cells sensitized in vitro to alloantigens, J. Immunol. 121: 1491–1495.PubMedGoogle Scholar
  31. Watson, J. D., 1979, Continuous proliferation of mutine antigen-specific helper T-lymphocytes in culture, J. Exp. Med. 150: 1510–1519.PubMedCrossRefGoogle Scholar
  32. Winchester, R., Fu, S. M., Wernet, P., Kunkel, H. G., Dupont, B., and Jersild, C., 1975, Regulation by pregnancy serums of non-HLA alloantigens selectively expressed on B lymphocytes, J. Exp. Med. 141: 924.PubMedGoogle Scholar
  33. Zarling, J. M., and Bach, R. H., 1979, Continuous culture of T-cells cytotoxic for autologous human leukaemia cells, Nature (London) 280: 685–688.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • Kendall A. Smith
    • 1
  1. 1.The Hematology Research Laboratory Department of MedicineDartmouth Medical SchoolHanoverUSA

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